CALIFORNIA TUMOR TISSUE REGISTRY
FIFTY- SEVENTH SEMI-ANNUAL SLIDE S~IINAR
ON
TIJMORS OF THE F~IALE GENITAL TRACT
MODERATOR:
RlCl!AlUJ C, KEMPSON, M, D, ASSOCIATE PROFESSOR OF PATHOLOGY & CO-DIRECTOR OF SURGICAL PATHOLOGY STANFORD UNIVERSITY MEDICAL CEllTER STANFOliD, CALIFORNIA
CHAl~lAN :
ALBERT HIRST, M, D, PROFESSOR OF PATHOLOGY LOMA LINDA UNIVERSITY MEDICAL CENTER L~.A LINDA, CALIPORNIA
SUNDAY, APRIL 21, 1974 9 : 00 A. M. - 5:30 P,M,
REGISTRATION: 7:30 A. M.
PASADENA HILTON HOTEL PASADENA, CALIFORNIA
Please bring your ~rotocol, but do not bring slides or microscopes to t he meeting, CALIFORNIA TUMOR TISSUE REGISTRY
~lELDON K, BULLOCK, M, D, (EXECUTIVE DIRECTOR) ROGER TERRY, ~1. Ii, (CO-EXECUTIVE DIRECTOR)
~Irs, June Kinsman Mrs. Coral Angus Miss G, Wilma Cline Mrs, Helen Yoshiyama ~fr s. Cheryl Konno Miss Peggy Higgins Mrs. Hataie Nakamura
SPONSORS: l~BER PATHOLOGISTS
AMERICAN CANCER SOCIETY, CALIFORNIA DIVISION CALIFORNIA MEDICAL ASSOCIATION LAC-USC MEDICAL CENlllR
REGIONAL STUDY GRaJPS: LOS ANGELES SAN F~ICISCO CEt;TRAL VALLEY OAKLAND WEST LOS ANGELES SOUTH BAY SANTA EARBARA SAN DIEGO INLAND (SAN BERNARDINO) OHIO SEATTLE ORANGE STOCKTON ARGENTINA SACRJIMENTO ILLINOIS
We acknowledge with thanks the voluntary help given by
JOHN TRAGERMAN, M. D., PATHOLOGIST, LAC-USC MEDICAL CENlllR VIVIAN GILDENHORN, ASSOCIATE PATHOLOGIST, I~TERCOMMUNITY HOSPITAL ROBERT M. SILTON, M. D,, ASSISTANT PATHOLOGIST, CITY OF HOPE tiEDICAL CENTER JOHN N, O'DON~LL, H. D,, RESIDENT IN PATHOLOGY, LAC-USC MEDICAL CEN!ER JOHN R. CMIG, H. D., RESIDENT IN PATHOLOGY, LAC-USC MEDICAL CENTER CHAPLES GOLDSMITH, M, D. , RESIDENT IN PATHOLOGY, LAC-USC ~IEDICAL CEUTER HAROLD AMSBAUGH, MEDICAL STUDENT, LAC-USC MEDICAL GgNTER N~IE-: E, G. APRIL 21, 1974 - CASE NO , l AGE: 47 SEX: Female RACE: Caucasian ACCESSION NO, 13759 CONTRIBUTOR: Shirley Howard, H, D. OUTSIDE NO. S- 2658-64 St, John's Hospital Santa Monica, California
TISSUE FROH: Vagina, left Bartholin' s gland
CLINICAL ABSTRACT: History: This 47 year old female noted pain in the left side of the vagina in the region of Bartholin' s gland for several months, lfhen she noted a hard nodule, she consulted her physician immediately. She bad a hysterectomy for carcinoma in situ of the cervix three years earlier. She had an abscess involving the right Bartholin 1 s gland at an earlier unkn01~n, date,
Physical examination revealed a stony hard 2 em, nodule possibly fixed to the dee·per tissues in the region of the left Bartholin 1 s gland. There was no obvious involvement of vaginal mucosa or of skin. The regional lymph lymph nodes were not palpable,
Radiograph: Cheat film ~1as negative, SURGERY: (June '17, 1964)
Excision biopsy was performed, followed by a radical bilateral vulvectomy on June 19, 1964 , GROSS PATHOLOGY:
The excision biopsy was a circumscribed, tan, very firm nodule, measuring 1,3 em , in diameter, The nodule bulged from the cut. .aurface of the left Bartholin's gland ~1hich was enlarged and measured 3 x 2.5 x 2 em ,
The vulvectomy specimen shOI FOLLOW-UP: (George Hummer, 11, D,) The patient was last seen and examined by her attending surgeon in August 1973 at which tiL1e a vaginal Papanicolaou smear was negative. The patient complained of occasional lower extremity edema that was controlled by the use of support type stockings. There was no evidence of malignant disease, Nfll.JE: L, N, APRIL 21, 1974 - CASE NO, 2 ·AGE: 64 SEX: Female RACE: Caucasian ACCESSION NO, 19905 CONTRIBUTOR: Stuart A, Monroe, M, D, OUTSIDE NO, S72- 7932 St, John's Hospital Tulsa, Oklahoma TISSUE FROM: Uterus CLINICAL ABSTRACT: History: This postmenopausal female presented with a three week history of light to heavy intermittent vaginal spotting. There was no contributory pastmedical or surgical history, Routine laboratory work was normal. A dilation and curettage revealed chunky, firm tissue fragments in association with a uterus which appeared to be "doubled" in size, SURGERY: (September 27, 1972) The uterus was distorted with a profile characteristic of uterine fibroids, A hysterectomy and bilateral salpingo-oophorectomy was accomplished with ease, GROSS PATHOLOGY: The specimen was a 340 gram uterus with attached adnexa. The uterine serosa ~1as unremarkable, The myometrium had several nodular leiomyom!ltous areas ~lith hemorrhage, necrosis, and "mucoid softening", The largest nodule was 8,0 em, in greatest dimension. A prominent submucosal necrotic nodule (2,5 em, in diameter) extended into the uterine cavity, The endometrium was otherwise unremarkable. The fallopian .tubes and ovaries Here normal. FOU.OW·UP: Patient was re-admitted on February 19, 1974 with recurrent pelvic mass and was scheduled for exploratory laparotomy (February 22, 1974). NAME: L, ~1 . APRIL 21, 1974 - CASE NO, 3 AGE: 60 SEX: Female RACE: Negro .J'ICCESSION NO, 955 9 CONTRIBUTOR: Ethel R, Nelson, ~1 . D. OUTSIDE NO. 57-3355 White Memorial Hospital Los Angeles, California TISSUE FRet!: Cervix CLINICAL ABSTRACT: This 60 year old Negro female presented 'dth h~o episodes of vaginal bleeding. Thirty years previously she underwent a bilateral salpingo oophorectomy as treatment for pelvic inflammatory disease. She never received any hormone replacement therapy. SURGERY : (August 2, 1957) A total hysterectomy was performed, GROSS PATHOLOGY : The uterus measured 7,2 x 5. 0 x 3,0 em, The endometrium measured 0. 1 em. in thickness and was slightly hemorrhagic. A 2.0 em. tumor , covered by intact mucosa, was present in the posterior lip of the cervix. The mass was light yellow with translucent areas and had the consistency of hard rubber. FOLLOI~ -UP: Thirteen months after surgery, a local recurrence developed in the vaginal cuff and was excised. The patient was then lost to follow up, NAME: L. z. APRIL 21, 1974 - CASE NO. 4 AGE: 12 SEX: Female RACE; FilLgino ACCESSION NO, 20440 CONTRIBUTOR: M, L, Bassis, M, D, OUTSIDE NO. SF 73-2151 Kaiser-Permanente Medical Center San Francisco, California TISSUE FRON : Right ovary .cLINICAL ABSTRACT: History: This 12 year old Filipino girl t~as in good health until one 1~eek prior to admission when slie noticed her abdomen ~1as getting larger and harder, She had not started menstruating and had no axillary hair. On physical examination there was a large hard fixed mass extending from the pelvis to the umbilicus, I Radiograph: An intravenous pyelogram shoWed a right hydronephrosis and hydroureter secondary to extrinsic pressure by a pelvic mass which also caused lateral displacment of the right ureter, A bone series t~as negative, SURGERY: (Febru~ry 20, 1973) A large right ovarian mass Has found, A total abdominal hysterectomy and bilateral salpingo- oophorectomy was performed, GROSS PATHOLOGY: The right ovary measured 18 x 16 x 10 em, and we.ighed 1500 grams , The mottled red-gray to yellm~ surface had bulging cysts containing clear watery yellcw fluid with an apparent intact capsule. The cut surface of the tumor disclosed a variegated pattern with multiple yellm·l lobules inter spersed with gray to red-bro~m necrotic zones admixed 1'1ith the cysts which measured up to 6 em, in diameter, The cysts contained watery or viscid yellow fluid and in some instances hemolyzed blood, The fallopian tubes, opposite ovary, and uterus sh~1ed no remarkable features, FOLLOW-UP: This patient received postoperative cobalt-60 radiation delivering 5,020 rads in 51 days which t~as well tolet:ated. She was asymptomatic and free of evident dis·ease until September 1973 when abdominal pain recurred, In early October, left lower quadrant masses and liver enlargement associated ~11th ascites were discovered, Chemotherapy with oral Cytoxan, IV vincristine, actinomycin D and mithramycin was started with rapid response. Five weeks after treatment began no masses were palpable abdominally or on pelvic eKamination, She remained ~Tell through mid-February 1974, She t ACCESSION NO. 20440 At autopsy there was 3. 5 liters of ascites and tumor covering the peritoneum. The tumor grew in tan grape-like clusters on the serosa. The cut surface was soft whitish tan and homogenous, A single adhesion was seen kinking the si~oid colon. Lymph nodes shewed two microscopic tumor· emboli, No abdominal organs bad intraparettchymal t\llllor except for mild degree of direct extension into the right lobe of the liver. There were no distant metastases. Superficial ~tress ulcer of the gastric fundus were seen, ~IE: I, C, APRIL 21, 1974 • CASE NO , 5 AGE: 57 SEX: Female RACE: Caucasian ACCESSION NO , 13317 CONTRIBUTOR: Daniel Krag, M, D, OUTSID!!: NO, R63- 32 Los Gatos Community Hospital Los Gatos, California TIS SUB FRQol: Cervix CLINICAL ABSTRACT: History: This 57 year old t~hite housewife, t~hose last normal menstrual period ~~as age 45, complained of watery vaginal discharge and intermittent spotting of blood for an unl SURGERY: On Janpary 8, 1963 an abdominal hysterectomy and bilateral salpingo• oophorectomy was performed, GROSS PATHOLOGY: The uterus was 10 x 5 x 6 em. The corpus was nodular and irregularly enlarged by several intramural fibroids, The entire cervical region was enlarged and thickened by an infiltrating pinkish yellow s ticky tumor that surrounded the endocervical canal, The cervical tumor measured 4,5 x 3.2 x 3.0 em, and extended to the margins of excision in the cervical region. There was evidence of cervical conization and curettement of the endometrial cavity, Both ovaries, oviducts and appendix were normal. FOLLOW-UP: Follow-up information not available, ~IE: H, S, APRIL 21, 1974 - CASE NO, 6 AGE: 60 SEX: Female RACE: Caucasian ACCESSION NO. 13900 CONTRIBUTOR: D, R, Dickson, M, D, OUTSIDE NO, S64-4386 Santa Barbara Cottage Hospital Santa Barbara, California TISSUE FROM: Vulva CLINICAL ABSTRACT: History: This patient had vulvar pruritus at irregu~ar intervals, The pruritus persisted despite medical treatment and became more intense, increased in frequency, and finally the patient noticed a ~7hite discolora tion of the vulvar skin. The last menstrual period was 10 years earlier, There was no vaginal discharge. She had never been married. One year , previously she had radiologic evidence of a peptic ulcer that responded to routine medication and diet, On physical examination she 1·7as normal except for several confluent white plaques that encircled the vulva, forming a ·horseshoe-shaped area with the clitoris in the central port·ion. Laboratory studies showed hemoglobin of 12, 4 gm, , WBC 7700, and a normal urinalys·is. SURGERY: A vulvectomy was performed on September 17, 1964, GROSS PATHOLOGY: The oval specimen was the clitoris and anterior portions of the labia majora and minora, measuring 115 x 50 x 10 mm. Irregular white plaques extended from the prepuce of the clitoris superiorly and laterally, and also to the medial aspects of each labia majora, a zone 35 x 25 mm, in greatest dimension. No ulceration or erosion of the skin or mucosa was evident,. COURSE: Because of apparent incomplete excision as determined by microscopic study, further excision '~as performed on October 1, 1964, removing an 80 x 30 x 17 mm. oval portion of skin and subcutaneous fat, with the linear r ecent healing surgical excision in the central portion. Page 2 APRIL 21, 1974 • CASE NO, 6 ACCESSION NO, 13900 the patient was free of disease for eight years. In November 1972, she returned to her surgeon with a few suspicious plaques, A biopsy showed the same disease with no underlying carcinoma, She was treated by ointments for o year and the lesion spread, Tbere is now erythema end skin thickening from the pubis to the anus and extending 1" on the medial aspects of both thighs, A radical vulvectomy including the clitoris is being considered. NAt-IE : M. C, APRIL 21, 1974 • CASE NO. 7 AGE: 36 SEX: Female RACE: Caucasian ACCESSION NO. 12799 CONTRIBUTOR: George Kypridakis, M, D, OUTSIDE NO, l•iNH 63-380 l•lhite Memorial Hospital Los Angeles, California TISSUE FRCN: Uterine fundus CLINlC/.L ABSTRACT: The patient was a single Caucasian female, gravida 0, who has been under medical care most of her life for grand mal epilepsy and mental retardation, An abdominal mass thought to be fibroids t·Tas first diagnosed in 1957. The familial history and remaining examination were negative, Her menses began at 18 years of age, occurred at 24-26 day interval and , lasted 4 days. SURGERY: An a~dominal hysterectomy was performed on January 29, 1963, GROS's PATHOLOGY: The total uterus measured 15 x 15.5 x 9 em . , ~Teighed 1200 grams, and included a pedunculated mass, 13 x 12 x 10 em. The serosa t·Tas covered by adhesions and there were small subserosal blebs filled with hemorrhagic fluid, In addition to the pedunculated tumor which had the ty~ical gross appearance of a leiomyoma, there were multiple intramural leiomyomata, the largest measuring 6, 5 em, in diameter, The latter presented a different gross appearance with a bulging cut surface composed of closely oriented multifaceted kernels of homogeneous yellow tissue, resembling kernels of corn. These were separated by siit· like spaces, The endometrial cavity was hemorrhagic and somewhat roughened due to previous curettage (done at surgery), The cervix <>as smooth t·Tith a nulliparous os. FOLLOH·UP: Patient is lost to follow-up, NAME: A, P, APRIL 21, 1974 - CASE NO, 8 AGE: 83 SEX: Female RACE : Caucasian ACCESSION NO, 12903 CONTRIBUTOR: John Blanchard, M, D, OUTSIDB NO, A63-25 Santa Barbara General Hospital Santa Barbara, California TISSUE PROH: Uterus CLINICAL ABSTRACT: History: The patient was first admitted on February 23, 1955 for epidermoid carcinoma of the uterine cervix, The diagnosis was made by cytology studies and biopsy, The patient was given radium impl ants and followed in clinic, In July 1955 she had a maxillary sinusotomy for chronic sinusiti~and in August 1960 she had sigmoidoscopy and intravenous pyelogram. She was treated for diverticulosi.s and diverticulitis, Rectal examination showed hemorhoida and a . pelvic examination was "deferred", Final admission was February 23, 1963 for bowel obstruction secondary to metastatic carcinoma of the uterus, At surgery, a huge mass filled the pelvis,,and many lymph nodes were involved with metastatic tumor, A colostomy was performed, She died suddenly on March 16, 1963, AUTOPSY: The pel vic mass was primarily an intrauterine tumor, The upper portion of the vagina was narrowed and thick walled, The canal of the uterine cervix was obliterated and the mucosa was thickened; o~ the anterolateral right quadrant there was a flat irregular plaque of dense neoplasm that measured up to 10 mm, in diameter, The uter ine fundus contained a polypoid gray white, granular, soft, polypoid tumor, measuring 6 em. in length by 3,4 em. in diameter, There was a 2 em, diameter focal zone of brown-red necrosis in the polypoid tumor, The wa l l of the uterus was thin (5 mm, ), The tumor had grown through the uterine wall and obliterated both adnexal structures. The adnexal tumors: cOliiD.unicated directl y with the lymph nodes in the pelvic area and to nodes adjacent to the lower aorta, Other aut opsy findings were right hydroureter, generalized arteriosclerosis, and peritoneal fibrous adhesions, NllME: I. C. APRIL 21, 1974 - CASE NO, 9 AGE: 24 SEX: Female RACE: Caucasian ACCESSION NO, 12998 CONTRIBUTOR: Hilliam P, Snider, ~1 . D. OUTSIDE NO, 596•63 Queen of the Valley Hospital !vest Covina, California TISSUE FR CLINICAL ABSTRACT: Riston:: Patient tias admitted on April 25, 1963 for the removal of a left ovarian cyst which had increased in size since discovered one year pre'liiously The patient was gravida I, para I, who delivered an infant in 1960, In 1961, a right ovarian cyst was removed elsewhere and the details sre not knot~n . She Qas had amenorrhea despite of cyclic hormone therapy, Physical examination: There was a movablE~ nontender, 6 c,m, mass in the left adnexal region. Laboratory data was normal and a pregnancy test was negative, SURGERY: A hysterectomy and left salpingo•oophorectomy was performed on April 26, 1963, GROSS PATHOLOGY: The uterus measured 10 x 6,5 x 4,5 em, in greatest dimension, The external cervical os was slightly roughened and irregular. The myometrium was tan and trabeculated and averaged 2,5 em, in thickness. Near the origin of the left tube, a 0,4 em. poorly delineated nodule bulged from the serosal surface, No other myometrial lesions were seen, The endometrial cavity was enlarged by a lobulated, yellowish tan tumor that measured 4 x 2,5 x 1.5 em, and was attached along the posterosuperior w,all, The tumor was partially cystic, friable , and blended into the underlying myometrium, The remaining endometrium tiaS a thin tan layer that measured about 1 mm, in thickness, The attached right 'tube was normal, The left ovary measured 6,5 x 5,5 x 5 em, and was multiloculated and cystic, The ovarian cyst linings were smooth ~nd only a small amount of ovarian tissue was found along one portion of the wall. FOLLO';I·UP: The patient was asymptomatic with normal pelvic examination and negative chorionic gonadotropin test up to 1968 when she toas lost to follow-up, IWIB: R. !1. APRIL 21, 1974 - CASE NO. 10 AGE: 15 SEX: Femal e RACE: Caucasian ACCESSION NO. 12802 CONTRIBUTOR : J , J . Bocian, 11. D, OUTSIDE NO, 563-578 Fresno Community Hospital Fresno, California TISSUE FROM: Ovary CLINICAL ABSTRACT : History: This young womarrwas in good health until one week prior to admission t~hen she had generalized lower abdominal pain, slight abdominal enlargement and abdominal tenderness on coughing. Menarche ~a s at age 12; her last menstrual period t~as 10 days prior to admission and t~as normal, although the fl~~ was l esa that usual. On physical examination, she was well developed and alert, but ill. The lower abdomen was moderately protuberant. There was a very hard, tender mess extending from the symphysis to the umbilicus. A second firm slightly tender mess was balloted in the epigastric area. On rectal examination, there was a herd smooth tender mass filling the pelvis. Labor atory report: Hemoglobin 11.5 gm?., WBC 12,300 with 63 segs, 25 lymphocytes, 4 monocytes, 2 eosinophile, and 2 basophile. Roentogenography: No calcifications were found in the abdominal tumors . SURGERY: (February 1963) An appendectomy and a bilateral a~lpingo • oophorectomy warn performed. GROSS PATHOLOGY: The left ovary weighed 630 gme., measnred 15 x 12 x 8 em., end was a solid fairly soft tumor that on cut section was smooth and light tan. There was some mucinous change, and a few cystic areas that measured up t o 2 em . The attached fallopian tube was normal. The right ovary was 800 grams ond similar to the left one. J1 small g-ray nodule was attached to the serosa of the Fallopian tube and there was anothe-r· nodule 0.8 em. in diameter attached to the mesosalpinx. POLL0\~-UP: The patient devel oped jaundice on ~1arch 2, 1963 (5ilirubin was 5.3 total) , She died in May 1963 and there was no autopsy. NAME: 0, A, APRIL 21, 1974 - CASE NO. 11 AGE: 51 SEX: Female RACE: Caucasian AcCESSION NO, 11497 CONTRIBUTOR: H, R, Fisher, U, D, OUTSIDE NO. 4748 Memorial Hospital of Glendal e Glendale, California TISSU)!: FROM: Uterus CLINICAL ABSTRACT: History: Patient had been feeling weak and "sick" for 4 years. She had a long history of dysmenorrhea, but for the past year menorrhagia was more severe and flow was extremely heavy, There had been almost continuous flow for three months prior to admission to the hospital in March 1961. I Physical examination was not remarkable other than pallor and obvious weakness. Pelvic examination revealed that vaginal bleeding . was present and a polyp protruded frcm the cervical os, The fundus appeared enlarged to 3~ times normal size. The adnexae were normal. SURGERY: On ~!arch 15, 1961, a dilatation and curettage was done and a large amount of yello~1 polypoid smooth material was obtained. A hysterectomy was performed. GROSS PATHOLOGY: The uterus measured 11, 5 x 9 x 7 em , and weighed 261 grams, The cervical segment measured 4 em, in length, The corpus and fundus were globular in configuration, On the serosal surface of the posterior aspect of the fundus there was a reddish tan nodularity covering an area of 1.5 em. in diameter area x 3 rom, in thickness. A similar serosal nodul arity of endometriosis was noted at the insertion of the left tube to the fundus. The entire fundus of the uterus was expanded diffusely to form an ill-defined tumor, measuring 7 x 6 x 5 em, The cut surface of the myometrium showed innumerable, soft, yellowish, nodular, well demarcated masses extending to the serosa l.'OLLOW -UP: She was seen in 1963 and advised she woul d need additional therapy. She was never heard fram again and at tempts to contact her in 1967 failed , NAME: M. G. APRIL 21, 1974 - CASE NO. 12 AGE: 62 SEX: Female RACE: Caucasian ACCESSION NO. 19913 COiiTRIBUTOR: Walter Coulson, ~t . D, OUtsiDE NO. 72S-5538 William H. Johnston, M, D. UCLA School of Med :1cine Los Angeles, California TISSUE FRCM: Ovary CLINICAL ABSTRACT: This 62 year old Caucasian female presented with a three week history of dull pain ond pressure in the left lower quadrant of her abdomen. Past history: The patient had a right oophorectomy at age 44 for o ( mucinous cystadenoma. SURGERY: (July 18, 1972) At laparotomy, a cystic left ovarian tumor woe found whi ch measured 7.0 em. in diameter. A total hysterectomy and left salpingo-oophorectomy was performed. The cystic tumor ruptured during the procedure. GROSS PATHOLOGY: The cystic mass weighed 140 grams . The inside of the cyst was lined with purple, friable papillar y material. In one portion of the wall was a lobulated, multicystic, white and yellow mass the size of a walnut. Gross and microscopic examination of the fallopian tube revealed no abnormality. The uter us showed multiple leiomyomas, mild proliferation of the endometrium and focal squamous metaplasia of the cervix. FOLLOiol -UP : As of February 1974 the patient is alive and the>:e is no evidence of either recurrent or metastatic tumor. IWIE: F. B, APRIL 21, 1974 - CASE NO, 13 AGB: 44 SEX: Female RACE: Caucasian ACCESSION NO. 19739 CONTRIBUTOR: Aaron A, Dubrow, !1 , 0 , OUTSIDE NO. P-72-127 Pacoima Memorial Lutheran Hospital Pacoima, California TISSUE FRat!: Uterine Cervix CLINICAL ABSTRACT: This 44 year old gravida VIII, para ~ Caucasian female was admitted for diagnostic procedures after a Papmicolaou smear revealed cells that were suspicious for malignancy. I PIIYSICAL EXA~IINA TION: There Has moderate uterine procidentia, The cervix was porous and the upper lip was extremely large, There were focal cervical erosions, The adnexae were normal, SURGERY: (January 26, 1972) A dilatation and curettage and a conization of the cervix uere performed, GROSS PATHOLOGY: The resected portion of the cervix measured 3, 4 x 2.4 x 1, 0 em, The epithelial surface was granular, On cut section ther e were multiple small cysts, measuring up to 0.3 em, , \1hich ~1ere filled with mucinous material, The tissue had a firm consistency, Microscopic examination of the uterine curettinga revealed prolifera tive phase endometrium and mild cystic changes, FOLLOW -UP: The patient received postoperative internal and external radiotherapy. As of February 1974 there is no evidence of recurrent or metastatic tumor. NAME: H• ..J . G. APRIL 21, 1974 • CASE NO, 14 AGE: 58 SEX: Female RACE: Unknawn ACCESSION NO, 20287 CONTRIBUTOR: Paul Thompson, M, D. OUTSIDE NO, 463·73 St. Lul CLINICAL ABSTRACT: This 58 year old gravida IV, pars IV , female was noted to have contact bleeding from the external cervical os during her annual physical examination, A biopsy of the cervix was obtained, In 1968 she had some irregul ar bleeding and an endometrial biopsy ' demonstrated proliferative hyperplasia, In 1970 because of some bleeding after stopping hormones, en endometrial biopsy was done and reported as negative, SURGERY: (March 7, 1973) A total hysterectomy ~lith a vaginal cuff and a bilateral salpingo oophorectomy was performed, GROSS PATHOLOGY: The entire specimen ~1eighed 180 grams, The cervix was extremely hard up to the endometrial junction, having the appearance and consistency of a raw potato, The endometrial mucosa and the myometrium appeared normal, Gross and microscopic examination of the fallopian tubes and ovaries revealed no significant abnormalities, P OLMJ~ UP: She was l ast seen on December 19, 1973 after a full course of cobalt, There was moderate lymph edema which was decreasing, There was no evidence of disease, NAME: V, E, G. A~RIL 21, 1974 • CASE NO. 15 AGE: 50 SEX: Female RACE: Caucasian ACCESSION NO, 20304 CONTRIBUTOR: John D, Silverthorne, M, D, OUTSIDE NO, DL-1621-73 Doctors Hospital of Lakewood Lakewood, California TI,SSUE FRCM: Uterus CLINICAL ABSTRACT: H-istory: This gravida I, para I, 50 year old female presented with menometrorrhagia of one year duration. Physical examination was essentially negative except that the uterus was 2 to 2% times nollllal size and consistent with a large fibroid uterus, Radiographs: Numerous radiolucent lesions suggestive o:f metastatic ' tumor involving many bones were seen on the chest radiograph and on : intravenous pyelogram, Mammography was negative, Laboratory report: Serum levels of calcium, phosphorus, and alkaline phosphatase were within normal limits, No myeloma proteins were detectable in the serum, A 24-hour urine for 5 hydroxyindole acetic acid (5HIAA) was well within normal limits, SURGERY: (August 20, 1973} A total hysterectomy and bilateral salpingo-oophorectomy was performed, GROSS PATHOLOGY: The uterus weighed 410 grams and measured 17 x ll x 7 em. The cervix had a few erosions. There were numerous submucosal and intramural leio myomas which measured up to 5 em. in diameter, One large intramural leiomyoma, located in the fundus, had a different appearance than the others. Although it was well delineated, on cut section it had a tan color, coarsely granular surface, serpigenous foci of hemorrhage and central cystic degenera• tion, The lesion was surrounded by a thin rim of overlying myometrium and serosa, and had no connection with the endometrium. Both fallopian tubes appeared grossly normal, The ovarie·s were also regular in gross appearance, both averaging 3 em, in maximua dimension, Sectioning of both revealed small cysts and corpora albicantia. Currently the patient is receiving intermittent treatment with alkeran and is able to do her own housework, NAI-IE: K, P, APRIL 21, 1974 - CASE NO, 16 AGE: 71 SEX: Female RACE: Caucasian ACCESSION NO. 11830 CONTRIBUTOR: T, C, Nelson, M,D, OUTSIDE NO, S-61-3472 Fresno Community Hospital Fresno, California TISSUE FROM: Endometrial cavity CLINICAL ABSTRACT: History: This 71 year old. Caucasian female presented with ·a history of intermittent vaginal bleeding of 8 months 1 duration. M~ no.pause occurred ftt age 53, The patient had been taking digitalis for the past 8 years for a he·art condition, Laboratory: A Papanicolaou smear was interpreted ss snowing atrophic changes. I SURGER¥: (July 1961) A hysterectomy and bilateral salpingo-oophorectomy was performed. GROSS PATHOLOGY: The uterus weighed 135 grams and measured 8,5 x 6,5 x 5 em. Hithin the endometrial cavity was a 4.0 x 2,5 em, mass of cystic, papillary and nodular tissue attached to the posterior and lateral ~1alls, The margins w.ere distinct and there wa·s no apparent invasion of the myometrium. The fallopian tubes and ovaries were. atrophic. FOLLOH-UP: As of 9 years post-surgery the patient had no symptoms referable to the gynecologic system. In 1970 the patient moved and has been lost to follow up, NAME: B. T. APRIL 21, 1974 - ChSE NO. 17 AGE: 25 SEX: Female RACE: Unknown ACCESSION NO. 20565 CONTRIBUTOR: Paul Herrmann, M, D. OUTSIDE NO. P 71-55 Alameda Hospital Alameda, Califcr nia nssUE FROM: Ovary CLINICAL ABSTRACT: History: This 25 year old· female presented with a four year history of irregular menses and periods of amenorrhea. A dilatation and curettage four years prior to admission revealed mild hyperplasia of the endometrium. Three years later (1970) a 3 em. left adnexal mass was noted, which slowly increased in size. Although she had been married for 7 years, she had not conceived, Physical examination: The breasts were normally developed, Pelvic examination revealed a 6 em. mass in the region of the left ovary. SURGERY: (1971) A left oophorectomy was performed, The surgeon reported that the uterus was slightly enlarged and boggy to palpation, The right ovary was small but normal in appearance, The left ovary was enlarged and bound d~~n to the posterior leaf of the broad ligament, The fallopian tubes ~1ere slightly nodular. GROSS PATHOLOGY: A solid bosselated, tan-yellow tumor, measuring 6 em. in diameter, replaced the left ovary. FOLLOW-UP: As of 3 years after surgery, tha patient is alive and well, NAME: E. A, APRIL 21, 1974 - CASE NO, 18 AGE: 43 SEX: Female RACE: Caucasian ACCESSION NO. 20562 CONTRIBUTOR: Roger Terry, ~~ . D, OUTSIDE NO, 74·2464 LAC-USC Medical Center Los Angeles, California TISSUE FRO.'!: Uterus CLINICAL ABSTRACT: History: This 43 year old craucasian female had regular menses until six weeks prior to admission ~1hen she developed continuous vaginal bleeding, Physical examination: There Has a fungating, friable, soft mass present ~7hich filled the upper vagina. No other abnormalities were found. { S:ORGERY: A bilateral salpingo-oophorectoiny and total hysterectomy· l~ss performed, GROSS PATHOLOGY: The shape of the uter.us was normal. The cervix 1~as replaced by a 6,0 x 6,0 x5.0 em, fungating, necrotic, papillary tumor, On opening the endocervical canal, the tumor tissue was seen to extend up to· the uterine cavity, The uterine cavity also contained three polyps, the largest measuring up t.o. 3. 0 em. Both ovaries and tubes 'tolere normal. IWIE: N. D. APRIL 21, 1974 - CASE NO, 19 AGE: 44 SEX: Fema l e RACE: Caucasian ACCESSION NO. 12141 CONTRIBUTOR: R. F. Hufner, M.D. OUTSIDE NO, E-445-62 Los Angeles, California TISSUE FRet!: Uterus CLINICAL ABSTRACT: History: This 44 year old gravida 0, para 0 Caucasian female complained of irregul ar menstrual periods · ~:~nd prolpnged ·heavy flow .ever since menarche. She stated that she never had a regular cycle. Physical Examination: The uterus was enlarged and to the left of the midline. SURGERY: (January 29, 1962) A total hysterectomy and bilateral salpingo-oophorectomy was performed. GROSS PATHOLOGY : The uterus '~eighed 131 grams and measured 11.8 x 5.2 x 4.4 em, Occasional serosal nodules, measuring up to 0, 6 em. , were present. The cervix was normal. The endometrium generally measured 0.1 em . in thick ness . There was a bulging, pink-tan 2 em. mess present in the fundus . The entire myometrium was speckled with innumerable slightly raised, grey•white areas, 0. 2 - 0,6 em. in diameter. Both ovar ies contained lesions which were interpreted microscopically as endometriosis. FOLLOW-UP: No information is available. ~IB: L, S, APRIL 21, 1974 - CASE NO, 20 AGE: 27 SEX: Female RACE: Caucasian ACCESSION NO , 20056 CONTRIBUTOR: Robert Silton, M, D, OUTSIDE NO. 73-8829 LAC-USC Medical Center Los Angeles, California TISSUE FROM: Uterus CLINICAL ABSTRACT: History.: This 27 year old·Caucasian 'female present.ed with a pelvic mass of 5 months' duration, A pregnancy test was negative; Past history: TWo years prior to admission a left mastectomy was pedormed after .a biopsy revealed malignant tumor, Onryear prior· to admission a right mastectcmy was performed when a similar tumor developed there. Laboratory report: A blood count showed a hemoglobin of 9.6 and ,a white cell count of 10,400 with 32 segmented neutrophile, 1 band, 39 lymphocytes, 2 mpnocytes, 1 promyelocyte and 25 blast forms, SURGERY: ~lay 29, 1973) At laparotomy a firm large pelvic mass was seen arising from the uterus and involving loops of small bowel, the sigmoid colon, and the side ~ GROSS PATHOLOGY: The tumor involved and markedly dis):orted the uterus and both ad.nexae (the ovaries ~1ere not recognizable as such), The mass was irregular, focally friable, focally necrotic and some areas contained thick gelatinous material. FOLLm-UP: Following surgery the patient received chemotherapy. As of February 1974 ah~ is alive and doing well, NAME: A. R. APRIL 21, 1974 - CASE NO. 21 AGE: 32 SEX: Female RACE: Caucasian ACCESSION NO. 20542 CONTRIBUTOR: Vivian Gildenhorn, M. D, OUTSIDE NO. 60-74 Inter-Community Hospital Covina, California TISSUE FR CI.INICAL ABSTRACT: This 32 year old gravida IV, para V, Caucasian female presented with almost content uterine bleeding of 3 months' duration, She had a long history of irregular menstrual bleeding. At the age of 17 she had undergone surgery for the removal of a "grapefruit" sized right ovaria·n cyst, SURGERY: (January 7, 1974) A total hysterectomy was performed, GROSS PA1ROLOGY: The uterus measured 9 x S x 3 em. and hod a normal contour, The ecto cervix was covered by ~1rinkled pink-tan mucosa, The endocervical lining and endometrial mucosa SRpeared diffusely hemorrhagic and focally roughened. The myometrium measured up to 2 em, in thickness. FOLL0l~-UP: Current follow-up is not available, ~!E: D, C, APRIL 21, 1974 - CASE NO, 22 AGE: 18 SEX: Female RACE : Caucasian ACCESSION NO , 20525 CON'l'RIBUTOR: David G, Porter, M, D. OUTSIDE NO. S72-2433 El Camino Hospital Mountain View, California TISSUE FR!M : Vagina CLINICAL ABSTRACT: History: This 18 year old-caucasian female presented Hith an 8 month history of mild premenstrual spotting and a recent episode of profuse vaginal bleeding, The remainder of the gynecologic history was non-contributory, Fcmilinl biotory: Patient's mother had been placed on l arge doses of diethylstilbestrol for the treatment of a threatened miscarriage at 13 weeks gestat ion. Physical examination: A papillary moss wit h superficial necrosis was evident in the upper third of t he vagina on the right lateral wall, The remainder of the pelvic examination was normal. SURGERY: Q:1arch 16, 1972) A total hysterectomy, partial vaginectomy, left salpingo-oophorectomy snd lymph node diosection were performed , GROSS PA Tl:IOLOGY: The vaginal tumor was dome-shaped, measured 1,5 x 1,5 em. , and contained mul tiple cystic spaces, measuring up to 0, 3 em. <~hich wer e filled with mucin, The lesion appear ed limited to t he superficial port ion of the vagina. The uterus, left ovar y , and left fallopian tube were normal. The thirteen iliac lymph nodes resected did not contain tumor , POLL(Koi·UP: As of 2 years post surgery, the patient remains well and totally asymp tomatic, N/IME: B. Z, APRIL 21, 1974 - CASE NO, 23 AGE: 18 SEX: Female RACE: Unknown ACCESSION NO. 20528 CON'lRIBUTOR: Paul Hiller, N, D. OUTSIDE NO. S73-5252 Kaiser llospita 1 Santa Clara, California TISBUE FRCl1: Ovary CLINICAL ABSTRACT : History: This 18 year old. female presented with abdominal discomfort and enlargement of one year's duration, She also complained of occasional amenorrhea . Physical examination: A huge pelvic moss was found which displaced the uterus, SIJRGERY: (1973) A right ovarian tumor was discovered at laparotomy. A solitary small peritoneal "implant" was noted in the pelvic cavity. GROSS PATIIOLOGY: The tumor was solid but demonstrated extensive hemorrhagic necrosis in all areas, except the periphery, The viable peripheral portions were pale gray to slightly yellow and semi-transl ucent, FOLLCM·UP: As of approximately 6 months follm~ing surgery, the patient has no evidence of recurrent tumor. NAHE: S. J. APRIL 21, 1974 - CASE NO. 24 AGE: 20 SEX: Female RACE: Caucasian ACCESSION NO. 20526 CONTRIBUTOR: David Porter, M, D. OUTSIDE NO , S72-l844 El Cmnino Hospital tlountain View, California TISSUE FR~I: Uterine Cervix CLINICAL AnSTRACT: This 20 year old gravida II, para I, Caucasian female had a 5-6 month history of post-coital bleeding. Cervical cytology done in "her early pregnancy '~as "atypical" and on pelvic examination there wer·e two discoid lesions over the cervix. SURGl!RY: (February 29, 1972) A cold knife cervical conization was performed at 14 weekt gestation. GROSS PAlt!OLOGY : A cireulor mass of cervix was ·present, the mos t peripheral portion of which was smooth epithelium, the entire remaining surface of which had a very velvety, somewhat papillary appearance . There were focal le.sions at 12, 6, 7, and 8 o"clock positions ~lhich ~1ere more plaque-like in appearance . This velvety appearance was rother granular and pale-yellmq throughout and elevat ed 0. 15 em, above the background of smooth portion epithelium. FOLLOli-UP: Labor was induced at 38 weeks' gestation for toxemia of pregnancy, a 7i lb, normal female infant was delivered, Both mother and child remained wel l as of January 28, 1974. NAl!lE: G. P. APRIL 21, 1974 - CASE NO. 25 AGE: 47 SEX: Female RACE: Unknotm ACCESSION NO. 20527 CONTRIBUTOR: Richard Kempson, ~1. D, OUTSIDE NO. 573-14798 s·tanfold University Nedical Center Stanford, California TISSUE FR~!: Ovary CLINICAL ABSTRACT: History: This 47 year ola female was first noted to have an abdominal mass during an admission for replacement of aortic, mitral and tricuspid valves. Following her cardiac surgery she was referred to a gynecologist in her home to1m but did not see him until one year later, At that time the mass had grown considerably larger. ' Physical examination: There was a soft, nontender, movable, smooth mass, 8 x 8 em. present in the left lower quadrant. By pelvic examination the mass seemed to involve the left adnexa and was movable and cystic. SURGERY: (1973) At surgery, a smooth cystic mass ~las seen occupying the left adnexa. There was no evidence of tUmor on the outside of the cyst and no evidence of tumor elsewhere in the pelvis or abdomen. A total hysterectomy and bilateral salpingo-oophorectomy was performed. GROSS PATHOLOGY: The mass measured 15 x 10 em. and had a smooth exterior, The interior contained sticky thick fluid and 1qas lined by innumerable yellow pink papillae varying from 0, 5 to 2. 0 em, in height. The left fallopian tube ~~as stretched over the mass. No residual left ovarian tissue was identified. The opposite ovary was normal. FOLLOW-UP: The patient is well as of three months postsurgery. NOTE: Slide 25 has two tumors , The papillary tumor belongs to Case 25 and ~to an error in preparation there is a piece of Case 17 also on the slide . ADDENDA CJ\LIFORNIA TUMOR TISSUE REGISTRY FIFTY-SEVENTH SEMI-ANNUAL SLIDE SEMINAR ON TUMORS OF 'l'!IE FEMALE GENITAL TRACT ~10DBRATOR: RICHARD L. KEMPSON, N. D. ASSOCIATE PROFESSOR OF PATHOLOGY & CO-DIRECTOR OF SURGICAL PATHOLOGY S TI\NFORD UNIVERSITY MEDICIIL CENTER STLINFORD, CALIFORNIA CHAI~IAN: ALBERT HIRST, M. D. PROFESSOR OF PATHOLOGY LOI>tA LINDA UNIVERSITY MEDICIIL CE~lTER LeMA LINDA, CALIFORNIA APRIL 21, 1974 PASADENA HILTON HOTEL PASADENA, CALIFORNIA TI\BLE OF CONTENTS CASE NO. ACC. NO. DIJ\GNOSIS PAGE General Discussion Case 3,5, 13 and 14: 1-5 3 19905 Adenoid cystic carcinoma of the cervix 15- 16 5 13317 Hell differentiated adenocarcinoma, cervix, cervical cell type 22-24 13 19739 Adenocarcinoma:of. cervix; mucinoos type. 50 14 20287 Moderately differentiated adenocarcinoma of endocervix ~lith scirrhous areas 51-53 l 13759 Adenoid cystic carcinoma of Bartholin gland 6-8 2 19905 Leiomyosarcoma of the uterus 9-14 3 9559 AdGnoid cystic carcinoma of the cervix lS-16 4 20440 Endodermal sinus tumor (yolk sac carcinoma) of the ovary 17-21 5 13317 Hell differentiated adenocarcinoma , cervix, cervical cell type 22-24 6 13900 Extra mammary Paget' s disease of the vulva 25-28 7 12799 Epithelioid leiomyoma present in spaces consistent with intravenous leiomyomstosis 29-30 8 12903 }lalignant mixed Mullerian tumor, heterologous type 31-33 9 12998 Syncytial endometritis (implantation site) 34-36 10 12802 Malignant lymphoma, unclassified (? Burkitt's lymphoma, ? ·poorly differentiated lymphocytic lymphoma diffuse) 37-40 ll 11497 Endometrial stromal sarcoma 41-44 12 19913 Malignant Brenner tumor of the ovary 45-49 13 19739 Adenocarcinoma of the cervix, mucinous type 50 14 20287 Moderately differentiated adenocarcinoma of the endocervix with scirrhous areas 51-53 Table of Contents Page 2 CASE NO. ACC. NO. DIAGNOSIS ~ 15 2030/o Metastatic malignant neoplasm, primary undetermined (a likely primary is breast) 54-56 16 11830 Papillary adenofibroma of the endometrium 57-58 17 20565 Sex cot:d mesenchymal tumor with annular tubules 59-62 18 20562 l'lullerian adenosarcoma of the uterus (hetero- logous element of rhabdomyosarcoma) 63-65 19 12141 Plexiform tumor (tumorlet) of the uterus 66-67 20 20056 Extramedullary myeloblastoma (granulocytic sarcoma, chloroma) 68-71 21 20542 Endometrial hyperplasia with intraglandular morules (metaplastic change) 72 -74 22 20525 Clear cell adenocarcinoma of the vagina 75-79 23 20528 Lm~ grade fibrosarcoma of the ovary 80-81 24 20526 Squamous papilloma ("Cockscomb polyp") of the cervix associated with pregnancy 82-83 25 20527 Serous tumor of borderline malignancy (low malignant potential) of tha ovary 84-86 (1) t.PRIL 21, 1974 General Discussion of Cases 3,5,13, and 14: These 4 cases represent different histologic types of adenocarcinoma of the cervix. Adenocarcinoma of the cervix may be subdivided into 2 major groups dependin8 on the cell of oriain: gland-cell carcinoma and reserve cell carcinoma (1). Gland-cell carcinomas represent approximately 57. of all carcinomas of the cervix and arise f r om the columnar cells ~hich cover the- endocervical surface and line the gland cleft spaces. There has been an apparent increase in the incidence of gland-cell carcinoma and they may represent as many as 10% of all carcinomas of the cervix. The second major category of adenocarcinoma of the cervix is the tumor arising from the subcolumnar reserve cells. These tumors often remain undiffer~ntiated or sh~1 mixed patterns of differentiation, Abell has classified the gland cell carcinomas as foll~~s (l) : 1. Cervical cell tYPe • • thi.s type of tumor has a true adenomatous appearance and consists of ~ell-defined alandular spaces formed by cclumnar or cuboidal cells. l1any of these tumors are lfell differentiated and have complex branching patterns reminiscent of that of the normal endocervix. Typically, the nuclei are enlarged, hyperchromatic, and variable in size, but often basibr in location. Hitoses are invariably present. The tumor alands are irregular and often have jutting sharp angles sometimes in a lobster claw configuration. Because adenocarcinoma of the endocervix can closely mimic the normal endocervilt, care· ful examination of the shape of glands and determining the presence of mitoses and abnormal nuclei is ah1ays indicated when examining the endocervix, The cervical cell carcinomas are divided into we~l, moderately, and poorly differentiated. 2. Hedullary carcinoma • is •the next most common type of cervical carcinoma and is composed of compact masses of neoplastic cells with little stroma. The gland formation is abortive and the cells are palisaded at the peri· phery of the cell nests, Clear cells can be present. This type of adenocarcinoma is often confused with squamous carcinoma. (2} liPRlL 21, 1974 3. PDpillary carcinoma - arises from the surface epithelium and the cells are arranged over papillary stalks resulting in a histologic pattern reminiscent of papillary serous carcinoma of the ovary. Mitoses are easily found and invasion is often super ficial. The prognosis is better than for the other types of adenocarcinoma. 4. Mucinous carci~oma - resembles mucinous carcinoma of the rectum and colon. The histologic pattern varies from tumor gland spaces filled with mucin and lined by cells having intracytoplasmic mucin to lakes of mucin containing float ing neoplastic cells. Signet ringfells may be present. Unless adenocarcinomD in situ is found,mucinous carcinoma may be difficult to separate from metastatic adenocarcinoma. 5. Bndometrioid carcinoma has a histologic pattern identical with, or very similar to, primary corpus adeno carcinomas. They are very difficult to separate from primary adenocarcinoma of the endometrium unless the entire uterus is available for examination. Usually, these tumors are well differentiated and may have areas of squamous metaplasia. 6, Scirrhous carcinoma - (poorly differentiated or anaplastic carcinoma of the cervix} encompasses most of the anaplastic and poorly differ entiated adenocarcinomas. Characteris tically, the tumor cells grm1 as indivi dual cells or in small cords and strands and infiltrating fibrous stroma . There is often intense stromal proliferation in response to the tumor cells. 7. Clear cell adenocarcinoma is the same neoplasm as found in the ovary, vagina, and endometrium. Formerly, ·these were tl1ought to be of mesonephric origin, but it is n~• appa rent that tho majority of them orise from Mullerian sources. There is a correlation bet:t APRIL 21, 1971~ Case 22. In additiol\ clear cell adeno carcincma may occur in ol der ,.,cmen and has e better prognosis than many of the other forms of carcinoma of the cervix. Histo logically, clear cell adenocarcinoma has a characteristic pattern ~lith tubules lined by clear to eosinophi l i c cells with hobnail or protruding nuclei. Clear cel l areas and papillary structures may also be present, as ~1e ll as a solid type of carcinomatous eret-lth. Reserve cell carcinomas are classified by Abell as follows: 1. Undifferentiated reserve cell carcinomas are composed of,small basaloid undifferentiated cells uith scant cytoplasm. Nitoses are frequent. These tumors ate often diagnosed ss poorly d~f£erentiated squamous carcinoma or undiffeTentiated carcinoma . 2. Adenosquamous carcinomas shows both squamous and glandular fferentiotion and both the squamous and glandular cocaponents are malignant. These tumors are often called mixed carcinomas and the 010 types of carcinoma may be mixed together intimately or may be infil trating in separate areas. Mixed carcinomQ~ spread rapidly to the regional lymph nodes. 3. Hucoepidermoid carcinomas :~re squamous carcinomas in tihich varying numbers of cells contain intracytoplasmic mucin. There are no clsndulsr formations. They appear to be more common in preenancy. 4. Adenoid cystic carcinomas .b:wc the hisi:oloci c appearances of adenoid cystic carcinoma elsewhere except that they frequently cgntain ar~as of squamous metaplasia and squamous carcinoma, as well as undifferentiated carcinoma . l hey are often lsrec and bulky and occur in an older age e;roup ,.,it h an average age in the sixties. Adenocarcinoma of the cervix (1,2,3,4,5) occurs at any average age of 52 , approximately five years hir,her than the overage age for squamous carcinoma. H01-1ever, the patients arc generally younger than t hose ~1ith adenocarcinoma of the endometrium. About three fourths of t he patients are over the age of fifty. Sociosexual f actors such as early age of intercourse, multiple sexual partners, and lm• socio-economic status are not of importance in adenocarcinoma of the cervix as they are in squamous carcinoma. The usual patient '·lith adenocarcinoma of the cervix, in fact, 18 more closely skin to the patient >~ith endome trial adenocarci noma. Patients with adeno carcinoma of the cervix most often present ,.,ith abnormal vaginal bleeding and one half of them ~·I ill have an exophytic or polypoid mass . In 15%, no gross (4) APRIL 21, 1974 lesion can be discerned; the remninder present as ulcero-infiltra tinc l esions. In general, gland cell catcinomas of the cervix are more aggressive than aguamous cell carcinoma of the ce~~~ or adenocarcinoma of- the endometrium, and have a metastatic spr ead similar to that of squamous carcinoma. Exten sion beyond the cervix occurs earl y and lymph node metastases are frequent, particularly in Stages II and III. In general, the f ive year survival stage for stage is 10-15'7. lnt·ler than for squamous cell carcinoma. The prognosis depends upon the stage of the t umor, the histologic type of adenocarcinoma, and, to s lesser extent, the grade of the carcinoma. Aa with squamous carcinoma, the le<•er the stage the better the survival. The histologic type of tumor seems to be important in determining the survival (6). Patients nith P!Pillary carcinoma, and the older female "ith clear cell carcinoma, definitely have a better prognosis t han paticntsllrtn more poorly differ entiated tumors (7). The poorest prognosis is •1ith .!.h..\! medullary, end?me trioid, and scirrhous types:--Tlle grade of the tumor "ithin each of the histOlogic- types is of some importance, houever it must be remembered that very well differentiated adenocarcinoma of the cervig con be ogSressive and some of the more poorly differentiated variet i es can be treated successful ly. In Abell's series, the cervical cell carcinomas represented 35% of the tumors and had a 3~ five year survival; medullar y carcinomas represented 21'7. of the tumors and had a 14'7. five year survival ; and papillary carcinomas represented 15% of the tumors and had e 57% five year survival. Squamous cell carcinoma can also be subclassified as to cell type, The bes t method of treatment of adenocarcinoma of the cervix has not been determined and both radiation and radical surger y are utilized. Overall, the survival is approximately 55% at five years and the survival Hill be altered by the prognostic factors discussed above. 1/hen adenocar cinoma is found in the cervix, the possibility of metastasis must be consi dered. One- t hird of the metastatic adenocarcinomas to the cervix "ill be from the endometrium. The next most frequent primary site will be ovary, folle<·led in order by colon, rectum, breast, and the genitourinary tract. REFERENCES: 1. Abell, M. R.: Invasive carcinomas of the uterine cervix. In: Norris, H. J., Hertig, A. T. & Abell, M. R. Eda: The Uterus, lAP monograph ffl4, Baltimore, 1973. The Niltiems and Wilkins Co. p. l>37. 2. Rombaut, R. P. et. al: Adenocarcinoma of t he cervig, A clinico-· patholocic study of 47 cases. Cancer ~-: 3 91, 1966. 3. Ab ell, M. R. and Goshinc , J . h. G: Gland cell (adenocarcinoma) carcinoma of the uterine cervix. Am. J. Obstet. & Gynecol. QJ;729, 1962 . (5) APRIL 21, 19711 ''· Kaaan, A. r.. et. al: Adenocarcinoma of the uterine cervix. Am. J. Obstet. & Gyoecol. 117:464, 1973. S. Tasker, J. T. & Collins, J. A: Adenocarcinoma of the uterine cervix. Am. J. Obstet. & Gynecol. 118:344, 1974. 6. Swan, D. S. and Roddick, J. H: A clinical pathologic correlation of cell type classification for cervical cancer. Am. J. Obstet. & Gynecol. 116:666, 1973. 7, Hameed, K: Clear cell carcinoma of the uterine cervix. Am. J. Obstet. & Gynecol. 101:954, 1968. I (~) APRIL 21, 197lt - CI\SE NO. 1 ACCESSION NO. 13759 MOD~RATOR'S DIAGNOSIS: Adenoid cystic carcinoma of the Bartholin's gland CLINICAL ABSTRACT: This l;7 year old female noted a hard nodule in the re!lion of the left Bartholin's gland. She had previously had an abscess involvine t he right Bartholin's gland at an earilier unkn~m dote. Examination revealed a stony hard 2 em . nodule in the re:;ion of the left Bartholin 1 s gland. l~hen excised the nodule was circumscribed, tan, very firm, and measur ed 1.3 em. A radical vulvectomy and bilateral node dissection was done. No tumor was found in any of the lymph nodes. NICRSCOPIC DESCRIPTION: The sections sh~1 an i nfiltrating t umor in ' ·1 hich the tumor cells are arranged in nests and cords with a microcystic pattern. The tumor cells are small, 'dth hyperchromatic nuclei, and scant eosinophilic cyatoplasm and are arranced in a pseudoacinar formation ar ound spaces containing eosinophilic hyaline-like material, fibrillar, eosinophilic material, or rarely basophilic mucoid material. The· hyaline is noted to be in continuity with similar material outside the cell nests. The tumor cells are surrounding cylinders of this material giving rise to the microcystic pattern noted at lrn·1 p01·1er . Tumor cells are noted around nerves and remnants of the Bartholin's gland. A PAS stain with a diastase digestion shows the hyaline material to stain inteoseLy wud emphasizes ita continuity with similar material in the stroma of the tumor. DISC'USSION: Recent ultrastructural studies have shntm that t he hyaline material in the cystic spaces of adenoid cystic carcinoma is basement membrane ma trix and not mucin (1). This basement membrane matrix is arranged in parallel arrays both in the pseudoacinar spaces and around the tumor nests. Tiny true acini can be found and are lined by tumor cell containing microvilli on their surface. The more empty appearing pseudoacini contain microfilaments of basement membrane material with stellate granules. Thu s, electro~ microscopy confirms that tho pseudoacini in adenoid cystic carcinoma are not glandular lamina but r ather are in continuity ~1it h the extra cellular space and contain basement membrane matrix arranged in a laminar fashion. The differential diagnosis in this case wou ld include basal cell carcinoma which may have an adenoid cystic pattern simulating adenoid cystic carcinoma and also may involve the vulva (2). However, the tumor in this case (7) Page 2 APRIL 21, 1974 - ChSE NO. 1 ACCESSION ~X>. 13759 sha~s none of the features of basal cell carcinoma such as peripheral nuclear palisading, atypical nuclei, and pleomorphism. In addition, basal cell carcinoma does not form pseudoacini containing basement membrane material. Secondly, one would want to consider adenocarcinoma, since poorly d.iffer entiated adenocarcinoma may have a gl andular pattern simulating adenoid cystic carcinoma. This would include adenocarcinoma of the Bartholin's gland, sweat gland carcinoma, adenocarcinoma of the urethra and metastatic adenocarcinoma . None of these tumors have the uniform tumor cells as seen in this case and none show the proliferation of tumor cells ' around hyaline cylinders. Metastatic carcinoma is an important entity in the vulva since it represents the third most f r equent type of malignancy of that organ (3) ., The most common primary metastatic tumor to the vulva is from the cervix, while adenocarcinoma of the endome trium and ovarian carcinoma are the next most frequent . The last consideration in the differential diagnosis would be hidradenoma papilliferum (4) . This is a benign tumor, almost invariably less thor. 2 em., and circumscribed. It has a papillary glandular pattern and contains both columnar and apocrine cells which arc not seen in the tumor in this case. It is a benign tumor of the apocrine glands limited to the genital area of the adult female. Carcinoma of the vulva represents 3-57. of all genital malignancies and carcinoma of the Bartholin's gland represents about 3-4% of all carcinomas involving the vulva. Carcinomas involving the Bartholin's glands are fairly evenly divided beo1een squnmous and adenocarci noma 1-ttb squamous carcinoma predominating in those t=ors arising near the orifice of the gland and adenocarcinoma more c011111on in t hose tumors from the deep acinar area (5). Carcinomas of the Bartholin's gland should ~ccur in the typical vulvar site, with the overlying skin intact, and contain residual Bartholin's gland tissue. All of these criteria may be impossible to establish in each case. The treatment of Bartholin's gland carcinoma is the same as other malignancies of the vulva, i.e., radical vulvectomy and bilateral nodal dissection. Adenoid cystic carcinoma occurs in a somewhat younger age group than other carcincmas of~e vulva and arises exclusively from tfie B!lrtholin's and-minor--vestibular g_!!lnds (0). It presents as a lump 1~hich is often pa inful, It may be confused clinically with an abscess or cyst. The histology is identical to that of adenoid cystic carcinoma occurriqgin other sites such as salivary gland, tracheal bronchial tree and the breast. The course is one of local recrudescence and progressive infiltration, often for long periods of time, and eventual metastases. The treatment is complete vulvectomy. Hhether the nodes should be removed is uncertain but most authorities advocate prophy lactic dissection. In Abell's series 25% of patients were :olive tumor free at 5 )tears, 25% were alive with tumor and 507. ;;ere dead \ Page 3 APRIL 21, 1974 - CASE NO, l ACCESSION NO, 13759 REFERENCES : l, Tandler, B: Ultrastructure of adenoid cystic carcinoma of salivary gland origin. Lab, Invest , 24:504, 1971. 2, Palladino, V, s., Duffy, J . L. and Burls, G. J: Basal cell carcinoma of the vulva, Cancer 24:4~ n . 1969. 3. Dehner, L: Metastatic and secondary tumors of the vulva. Obstet. & Gynecol. 42:47, 1973. 4. Woodworth, H. et. al: Papillary hidradenoma of the vulva: A study of 69 cases. Am. J. Obstet. Gynecol . !1Q:50l, 1971. 5, Barclay, D. L,, Collins, C. G. , and Macey, H. 8.: Cancer of the Bartholin's gland, Obstet . and Gynecol. 24:329, 1964. 6, Abell, M. R,: Adenocystic basal cell carcinoma of vestibular glands of vul va, Am. J. Obstet. Gynecol. 86:470, 1963. 7. Tchang, F. et. al: Adenocarcinoma of Bartholin's gland .associated 11ith Paget 's disease of the vulvar area. Cancer 31:221 , 1973. (9) APRIL 21, l97t, - CASE NO. 2 ACCESSION NO. 19905 !10DERATOR 'S Dll\GNOSIS: Leiomyosarcoma of the uterus . CLI NICAL ABSTRA.f!: This 64 year-old female had a three l·loek history of vaginal bleeding . h n&C revealed chunky fit~ tissue fragments and an enlarged uterus. The hysterectomy specimen contained several nodular masses with hemorrhage, necrosis, and mucoid softenin~. The larzost mass measured 8 em . in diameter. ~UCROSCOPIC DESCRIPTION: This tumor is composed of cells with vesicular, irregular nuclei and eosinophilic to clear cytoplasm. In some areas the tumor cells appear 1 cuboidal, ~1hile in others they are spindled. Giant cells are present: as are large cells with bizarre pleomorphic nuclei. Areas of necrosis are frequent, and surrounding areas of necrosis, the t umor cells are closely paclted and spindled. Some of the tumor cells with clear cytoplasm have an epithelioid arrangement; hat~eve r, the overall impression is thai: of a mesenchymal tumor. Hyalinization is prominent. ~litos es are frequent and some are abnorntal. t1itotic counts revealed some areas of the tumo.- to contain over 20 mitoses per 10 hir;h power fields. A trichrome stain sh~IS irre::;ular collanen present in the tumor but most of the tumor cells have red cytoplasm. t. P'rt1H stai n failed to reveal myofibrils. DISCUSSION: This neoplasm is somewhat difficult: to definitely classify as orieinatinc from smooth muscle; hooever, the e longated and relatively clear tumor cells as 1·1ell as the arrangement of the tumor cells indicates to me that this is a leiomyosarcoma. The pattern is not that of endometrial str~ual sarcoma and there is no evidence of cross striations or bone formation. When a sarcoma is found in the uterus, malignant mi> Sarcomas of the uterus are relatively rare but pose problems in diagnosis and classification. He use a modification of the classification suggested by Ober 1·1hich is reproduced in Table 1 (1), Pure sarcomas are those (10) Page 2 APRIL 21 , 1974 • CASE NO, 2 /1CCESSION NO, 19905 ~hich contain only one type of sarcoma, and the sarcoma is considered homologous if the tumor is differentiating towards structures normall y found in the uterus, such a s smooth muscle or endometrial str oma. The sercoma is considered heterologous i f it is differentiating into tissues not normally found in the uterus such as bone or skeletal muscle. Nixed sarcomas contain 'more than one type of sarcoma and may be either homologous or heterologous. The third major group of sarcomas are the mal ignant mixed Mullerian tumors which cont:ain sarcoma and c ar'cinoma . The sarcoma may l>e any of several types and it is common to have several sarcomas mixed to3ether in the same tumor. The carcinoma may be either adeno, squamous, undifferentiated or combin.ations of these three. The malignant mixed Mullerian tumors are subclassified as to <~hether the sarcomatous element is homologous or heterologous. In much of the recent literature the homologous tumors are called carcinosarcomas and ~e heteroloBous tumors are designated as mixed mesodermal tumors. A simpler classification of the uterine sarcomas t~hich includes only the cO!Mlonly encountered types is presented in Table 2. The major problem in d i agnosing smooth muscle tumors of the uterus is separating leiomyoma from leiomyosarcoma (1,2,3,4). Many different criteria have been advanced and there is still controversy about the relotiv~ value of each of these (l,Lf) In our e:tperience, the number of mitoses per 10 high p6wer fields is the single most important criteria for separating benign from rnalignant uterine smooth muscle tumor (1). Obviously, any tumor which has infiltreted contiguous organs, or t~hich has invaded blood vessel s and is not intravenous lciomyomstosis, must be considered malisnant. We also think that any smooth muscle tumor of the uterus which contains over 10 mitoses in 10 high po\·ler fields is malignant r egardless of other histologic feot~>res. Any smooth muscl e tumor which contains l e ss than one mitoses in 10 high power fields is benign regardless of the degree of pleomorphism or the presence of giant cells, Tumors which contain betHcen 1 at1d 10 mitoses per 10 high pot-1er fields are more difficult and are considered to be neoplasms of uncertain malignant potential. I t bas been our experience that tUlllors with 5-10 mitoses and pleomorphism cen be aggressive and we desiznate them as leiomyosarcomas. Tumors t~ith 5-10 mitoses and no pleO!ilorphism or atypia He designate as borderline malignant as '~e do tumors uhich contain 1-5 mit:oses in 10 high pm1er fields and are pleomorphic. ~le mus t accep t the fact that there are borderline smooth muscle tumors f or 1·1hich t·le cannot be ce rtain of future behavior. The number of such smoo th muscle tumors is sma ll and most smooth muscle turaors can be accu~ately diagnosed using mito tic counts as outlined above. It must be emphasized that a t least 8 or 10 sections of every quest ionabl e smooth muscle tumor should be tal Pane 3 APRIL 21, 197l• - CASE NO. 2 ACCESSION NO. 19905 ~le consider leiomyomas 1·1ith borderline mitotic counts ss described above to be of uncertain CJalignant potential and use the designation atypical leiomyoma of borderline malignancy. He use the term atypical for leiomyomas which contain bizarre cells, atypical cells or giant cells but do not demons trate sufficient mitotic activity to be considered malignant or of borderline malignancy. We use the term cellular leiomyoma for those tumors 1~ithout pleomor phism or i ncreased mitotic activity Hhi.ch contain large numbers of cells closely packed together (6). The ter m bizarre leiomyoma is reserved for those smooth muscle tumors 1·1ith unusual histolo&ic appearances such as leiooyoblastana, clear cell leiomyoma and epithelioid cell leiomyoma. These are discussed in Case 7. Finally there is a lesion ltn~10 as benign metastasizing l eiomyoma (7). This is a histologically benign smooth muscle tumor >1hich metastasizes. There is no kn01m uay to separate these frcrn 1 l eiomyomas and they cannot be accurately diannosed by present criteria. Fortunately they are extremely rare. Pa tients with leiO!liYosarcoma may be i n their twenties to old age . The most common SYNptom is abnormal vaginal bleeding. The tumors usually are soft gray -~1hite -t an ~lith bulging surfaces but may be hemorrhagic and necrotic. Hhen examinin::l hysterectomy specimens, all grossly unusual ntyomas should be sectioned, Leiomyosarcoma in the uterus is often solitary but may be sssociated ~lith other myomas else1~here in the uterus. In our experience leiomyosarcomas do not arise within benign l eiomyomas . Microscopically leiomyosarcomas demonstrate a wido range of patterns, the most common of 11hich is spindled cells closely pocked tocether '~ith large numbers of mitoses. Bizarre and anaplastic cells msy also be present. Giant cells may be found in either benign or mali gnant smooth muscle tumors. Cytoplasmic nuclear inclusions are commonly found in leiomyosarcomas and may be helpful diagnostically. r~e prognosis of leiomyosarcoma de pends upon the extent of the tumor, the mitotic activity, the extent of infiltration of contieuous organs and the length of time the patient has had the tumor. Age is also a significant factor su1ce premenopausal women have a be tter prognosis than post menopausal. The treatment is surgical and the overall survival is approximately 207. at 5 years. ln summary, most smooth muscle tumors of the uterus can be accurately diagnosed by carefully performed mitotic counts . There are a fe1-1 tumor s 1~ith equivocal mitotic activity and uncertain malienant potential but these represent a very small percentage of t he smooth muscle tumors occurring i n the uterus. It must be empha s ized that the use of mitotic counts for diagnosis as outlined above applies only to sCJooth muscle tumors of t he uterus, not smooth muscle tucors originatine in other organs. \ (12) Page 4 APRIL 21, 1974 • CASE NO. 2 ACCESSION NO. 19905 REFERENCES: 1. Kempson, R. L.: Sarcomas end related lesions, In: The Uterus. IAP monograph l?l4 Ed . : Norris & Hertig p. 298. tHlliams & ~lilkins Co . , Baltimore, 1973. 2. Cbristophcrso9, W. M., et al: Leiomyosarcoma of the uterus. Cancer 29: 1512, 1972. 3. Taylor, H. D. and Norris, H. S.: Diagnosis and prognosis of leiomyo sarcoma . Arch. Path. 82:40, 1966. 1;.. Silverberg, S. G.: Leiomyosarcoma of the uterus. Obstet. & Gyneco}. 38: 613, 1971. 5. Fechner, R. E.: Atypical leiomyomes and synthetic progestogen therapy. Am . J. Clin. Pathol. 49:697, 1968. 6. Perenczy, A. , et ol: A comparative ultrastructural study of leiomyo sarcoma, cellular leiomyoma, and leiomyoma of the uterus. Cancer 28: 1004, 1971. 7. Spiro, R. H. and McPeak, C. J.: On the so~called metastasizing leiomyoma. Cancer 19:544, 1966, (13) Page 5 APRIL 21, 1974 - CASE NO. 2 ACCESSION NO. 19905 Table 1 Classification of Uterine Sarcomas I, Pure sarcomas A, Pure homologous 1. Leiomyosarcoma 2, Stromal sarcoma 3, Endolymphatic stromal myosis 4 . Angiosarcoma S. Fibrosarcoma B, Pure heterolos ous 1. Rhabdomyosarcoma (including sarcoma botryoides) 2. Chondrosarcoma 3. Osteosarcoma 4. Liposarcoma II. 11ixed sarcomas A. Mixed homologous B. Mixed heterologous Mixed heterologous sarcoma s "ith or l~ithout homologous elements III. Malignant mixed Mullerian tumors (mixed mesodermal tumors) A. 11alignant mixed Huller ian tumor, homologous type Carcinoma plus leiomyosarcoma, stromal sarcoma or fibrosarcoma, or mixtures of these sarcomas B. Malignant mixed }lullerian tumor, heteroloeous type Carcinoma plus heterologous sarcoma t~ith or ~lithout homologous sarcoma IV, 11ullerian adenosarcoma (See Case 18) V. Sarcoma, unclassified VI, }Ia lignant lymphoma (14) Page 6 APRIL 21, 1974 - CASE NO, 2 ACCESSION NO, 19905 Table 2 Simplified Classification of Uterine Sarcomas I . Leicmyosarcoma II. Malignant mixed Muller1an tumor with or without heterologous elements III. Endometrial stromal sarcoma A, Low grade stromal sarcoma (endolymphatic stromal myosis) B. Stromal sarcoma IV. Malignant lymphoma v. Rare specific types VI , Sarcoma unclassified Table 3 Histologi· Features of Benign and Malignant Smooth Huscle Tumors of the Uterus I. Histologic features indicative of leiomyosarcoma A. Greater than 10 mitoese in 10 HPF with or ~Jithout: cellular pleomorphism B, Mitotic activity of 5 to 10 mitoses in 10 HPF with cellular pleomorphism C. Extrauterine infiltration into contiguous structures II. Histologic features indicative of lei omyoma A. Less than 1 mitosis per 10 HFF regardless of the presence or absence of cellular pleomorphism. B, Less than 5 mitoses in 10 HPF if tumor cells are not pleomorphic III. Histologic features in smooth muscle tumors of uncertain malignant potential A. 5 to 9 mitoses in 10 HPF without cellular pleomorphism B, 1 to 4 mitoses in 10 HPP with significant cellular pleomorphism (15) APRIL 21, 1974 • CASE NO. 3 ACCESSION NO, 9559 MODERATOR'S DIAGNOSIS: Adenoid cystic carcinoma of the cervix. CLINICAL ABSTRACT: this 60 year old patient presented with 2 episodes of vaginal bleeding. A hysterectomy was performed and a 2 em. tumor covered by intact mucosa was present in the posterior lip of the cervix. The mass was light yellow and hard :thirteen months after surgery a local recurrence occurred in the vaginal cuff and was excised. the patient was lost to foll~•·up . MICROSCOPIC DESCRIPTION: The cervix is infiltrated by a carcinoma with a histologic pattern , identical to that seen in the vulvar lesion in case 1. Cords and nests of uniform cells are forming pseudoacinar structures by encompassing cylinders of hyaline basement membrane matrix. In addition to the adenoid cystic areas, there are areas of squamous differentiation with nests of blond looking squamous cells as well as nests of undifferentiated basaloid carcinoma and histologically malignant squamous cells. Large portions of the tumor are composed of hyaline matrix containing cords of solid cells. DISCUSSION: The differential diagnosis of adenoid cystic carcinoma of the cervix should include microglandular hyperplasia which occurs in patients taking contraceptive medications and in pregnant patients (1). Microglandular hyper plasia is characterized by crowded small glandular spaces containing mucus with polys and lined by flattened bland appearing cella. The lesion may protrude above the cervix. the pseudoacinar and cylindromatous pattern of adenoid cystic c~rcinoma is not present. Microglandular hyperplasia is invariably found in the superficial portion of the cervix. Mucification of the cervical glands, in which there is inspissation of secretion such that the endocervical glands appear to contain colloid, can also superficially resemble adenoid cystic carcinoma but the cells are flattened endocervical type cells, not the basoloid cells seen in adenoid cystic carcinoma (1). Hesonephric remnants are found in the lateral portions of the cervical stroma and are composed of tubule-like structures lined by cuboidal epithelium which often contain central eosinophilic material. the cells do not resemble the basaloid cells of adenoid cystic carcinoma and cylinders of hyaline material are not found in the lumens . Adenoid cystic carcinoma of the cervix (2, 3,4) occurs in older women than moat other types of adenocarcinoma of the cervix, the average patient being in her 69's. there are no choroctoristic symptoms and most patients present (16) Page 2 APRIL 21, 1974 • CASE NO, 3 J\CCESSION NO. 9559 with vaginal bleeding. It is an uncommon tumor with only about 36 cases previously reported. On physical examination there is always extensive erosion and ulceration, and the tumors are often large and bulky. There has usually been extensive grO<~th >~ithin the cervix before symptoms and the tumor is often visable, Microscopically, these tumors are frequently associated with either overlying squamous carcinoma-in- situ or dysplasia of the cervical epithelium or with invasive squamous cell carcinoma, adenocarcinoma or undifferentiated carcinoma. A~out 1/3 of cervical adenoid cystic carcinomas will contain. areas c. ·: aquall\ous cell carcinoma, Adenoid cystic carcinoma infiltrates the stroma of the cervix and other nearby tissues extensively and lymphatic permeation is common. The tumor is thought to arise in the reserve cells beneath the columnar mucinous epithelium. Since these cells can differ entiate toward both squamous and columnar types of epithelium either typQ of differentiation may be seen in reserve cell carcinomas. Unlike adenoid cystic carcinoma in other locations, the cervical tumor is probably not a distinct pathologic entity but part of the spectrum of reserve cell carcinoma. Adenoid carcinoma of the endometrium has also been reported, but is very rare. In summary, this is a case of adenoid cystic carcinoma of the cervix. There have been approximately 36 reported cases and these tumors ore thought to arise from the reserve cells of the cervix. They are almost always mixed with other types of carcinomas and are probably not a distinct pathologic entity. REFERENCES: l. KyrioJs.oo , ~1., Kempson, R.L. and Konil 1 . ~tiles , P.A. ond Nori$, 'R.J.: Adenoia cystic carcinoma of the cervix. Obstet. & Gynec, 38:l03, 1971, 3. Gallager, H.E . ct al.: Adenoid cystic carcinoma of the uterine cervix. Cancer 27:1398, 1971. '•· Gordon, H . ~l . et al: Adenoid cystic carcinoma of the uterine cervix. Am. J. Clin. Path, 58:51, 1972, (17) llPRU. 21, 1974 - CllSE NO. 4 ACCESSION NO. 20440 MODERATOR'S DIAGNOSIS: Endodermal sinus tumor (yolk sac carcinoma) of the ovary) CLINICIIL ABSTRACT: This 12 year old prepubertal Filipino girl noted that her abdomen was getting larger and harder. Examination revealed a large fixed mass extending from the pelvis to the umbilicus. At surgery, the right ovary was replaced by a tumor measuring 18 x 16 x 10 em. and weighing l500 gms. The tumor had a mottled red-gray-yellow surface with bulging cysts containing cl ear yellow fluid. The solid portion of the tumor was var igated with multipl e yellow lobules interspersed with gray to red-brown necrotic zones. Postoperatively, the patient r eceived radiation. However, within a few months she had extensive. metastatic tumor and died approximately one year following her otiBinsl surgery. At autopsy, t here was ascitts• and tumor covering the peritoneum. The t umor grew in grape-like cluster~ from the serosa. There were no distant metastases. HICROSCOPIC EXAMINATION; This tumor is composed of small cells with basophilic nucl ei which form• a loose vacuolated network of spaces of varying sizes and shape& .. .:l1o~e solid er~as are present ond contain cystic ueas lihich are lined by cuboidal tumor cells. The overall appearance is that of a labyrinth of interconnecting sinuses. At one edge of the t umor there are honeycombed areas lined by flattened mesothelial-like cells interspersed within a myxoid stroma. Throughout the tumor there are eosinophilic globules which are PAS positve after diastase digestion. These globules are both intra and extracellular and are of varying sizes. In the section available in the set, yolk sac structures oro not found; hm~ever, in other sections characteristic palisading of tumor cells about mesenchymal tissue containing a central capillary arc present. Hitoses are very numerous. DISCUSSION: The differential diagnosis of endoderrnal sinus tumor must always include clear cell adenocarcinoma . Schiller in 1939 described both clear cell carci noma ond the endodermol sinus tumor under the cateeory of mesonephroma , and these two tumors have been frequently confused tiith one another for the past thirty five years. Clear cell adenocarcinoma, which occurs in the ovary as well as other sites , can be dif ferentiated f r om endodermal sinus t umor because it has a tubular pattern and the tumor cell nuclei, \lhicb are hyperchromatic, often appear to be extruding from the tumor cells. Th..: network pattern note•· in endodermal sinus tumor is not present in the clear cell adenocarcinoma, Both (18) Page 2 hPRIL 21, 1974 - CASE NO. 4 hCCESSION NO. 20440 tumors may have clear cells, however, and structures resembling glomeruli can b:e found in both,itmmors. ' The P.AS pos.itive 110sinophilic globules found in endodermal sinus tumor are not present in clear cell carcinoma. Most importantly, the yolk sac pattern of palisaded endodermal cells about vessels is not seen in clear cell carcin~a. Endodermal sinus tumor must also be separated from the embryonal carcinoma of the adult testicular type which has only rarely even been encountered in the ovary. Embryonal carcinoma of the adult testicular t ype is composed of pleomorphic cells arranged in sheets or o sy_ncytium with a gland-like pattern rather than the ne~•ork pattern noted in endodermal sinus tumors. The tumor cells in the endodarmal sinus tumor are small cuboidal, columnar, unlike the large anaplasticcells characteristically found in embryonal carcinoma. Teilum first recognized the germinal origin of the endodermsl sinus tumor o~d its reproduction of extra-embryonic yolk sac structures (1,2). Figure 1 from. Pierce and Teilum sh~•s current concepts of the differentiation of germ cell neoplasms for both ehe ovary and the testicle (1,3), The primitive germ cells may differentiate as germ cells ziving rise to seminomas and dysgerminomas. They may remain primitive and undifferentiated, giving rise to the adult testicular type of embryonal carcinoma, Embryonal carcinoma cells may differentiate to either, embryonic structures, giving rise to a teratoma, or, extra-embryonic structures, giving rise to tumors of the placenta and yolk sac, namely choriocarcinoma and endodermal sinus tumor . This scheme is supported by experimental work of Pierce (3) lfho bas sh011n that experimental teratocarcinomas will differentiate into yollc soc (extra-embryonic) type of structures when ::;r01m either in vitro or ascitic fluid. Endodermal sinus tumor may be associated with, or mixed with, teratoma indicating its close relationship to embryonic structures, Thus, experimental models support the germ cell origin of this croup of tumors and the morphologic evidence that they may differentiate to extr~·embryonic structures, Endodermal sinus tumors also occur in other sites than the ovary. They have been reported to arise in the retroperitoneum, the saccrococcygeal area, the anterior mediastinum, the pinealr the vagina, and the testicle. They occur both in the infant testicle and the adult testicle and have a different prognosis dependine on the age of the patient, In the infant testicle, endodormol sinus tumors have also been designated as orchioblastoma or adeno carcinoma of the infant testicle and have a relatively good prognosis of approximately 651. at five years. In the adult testicle, the tumor is very rare ond is liiSJly metastatic with a poor prognosis. Drs, Huntington and Bullock have pointed out the similarities of the endodermal sinus tumor in the testicle and the ovary ond have concluded that both tumors are ~f similar orf8in (4). Endodermal sinus tumor is the most common expression of embryonal (19) Page 3 APRIL 21, 1974 - CASE NO, 4 ACCESSION NO. 20440 carcinoma in the ovary '~here as it is unusual and rare in the adult testicle. The adult embr yonal carcinoma on t he other bend is extremely rare in the ovary and common in the adult testicle. In the infant testicle, endodermal sinus tumor is the most common expression of the embryonal carcinoma. Endodermal sinus tumor in the ovary occurs in a sharply limited range from two to forty years (5,6). The average age is ~~enty end the symptoms ere the result of en expending mass, namely pain onda protuberant abdomen. Occasionally, the tumors will rupture and result in acute abdominal pain. They are usually unilateral with only about 5~ bilateral incidence. Grossly, they ere usually larze tumors measuring from 5 to 30 cme, thinly capsulated, nodular, and multicystic. On the cut surface, there is extensive hemorrhage and necrosis alternating with yellowish areas. The fluid in the cyst is, yell Histologically, one or more of the following patterns will be found (1): 1. A loose vacuolated network with cystic spaces lined by flattened cells. PAS diastase resistant globules are present both intra and extracellularly. This pattern is present in all endoderma1 sinus tumors end is usually predominant. 2. Endodermal sinus structures consistinz of a vessel surrounded by mesenchyme which, in turn, is surrounded by palisaded endo derma1 cells. This entire structure is osually within a cystic space l·lhich is surrounded by endodermal cella. This structure is similar to the yolk sac of the rat embryo end gives the tumor ita name . 3. On some occasions cystic structures festooning in a complex fashion and lined by cuboidal cells can be found. These are endodermal sinuses and some of the cells may show mucinous differentiation. 4 . Compact aggregates of undifferentiated embryonal cells. In all tumors mitoses are frequent and one may find giant cells. As noted above·; the endodermal sinus tumor may be associated with embryonal carcinoma, teratoma, dysgerminoma, and teratocarcinoma. The therapy for endodermol sinus tumor is usually surgery followed by radiotherapy. The prognosis is practically hopeless with only a feN \(nown survivors. The value of chemotherapy has not been fully explored. (20) Page 4 APRIL 21, 1974 • CASE NO, 4 ACCESSION NO, 20MO Recently the ~lorl d Health Organization has adopted a classification of ovarian t umors which should become the standard for ovarian tumor nomenclatura (8). The germ cell tumors represent one of the the major subtypes of ovarian tU!IIors and our working classification of the germ cell tumors based on the tffiO classification is reproduced below. Of interest and importance is that the teratoma group has been divided into mature and immature types, The mature tumors consist exclusively of adult structures, while the immature teratanas contain embryonal tissue, almost al\~ays "ith mitoses. !4ature cys tic t"erat anas are benign except for the rare instances of carcinomatous and sarcomatous transformation. The ma ture solid teratomas of the ovary are also almost invariably benign unlike the solid mature teratomas of the testis 1~hich are frequently malignant (9) . Immature teratomas, whether solid or cystic, must be considered malignant and care must be tal Classification of Germ Cell Tumors of the Ovary (l~orld Hea lth Organization) (8) A. Dysgerminoma B. Endodermal Sinus Tumor (yolk sse carcinoma) C. Embr yonal Carcinoma D. Choriocarcinoma E, Teratomas l. Immature 2 . Mature a). Solid b) . Cystic (with and without malignant transformation) 3. Highly Specialized a), Strums ovsrii b) • Carcinoid c), Stromal carcinoid d) , Others F. lUxed Forms . REFERENCES: l. Teilum, G.: Special Tumors of Ovary and Testis, Phila. 1971. J.B. Lippincott Co , 2. Teilum, G, : Classification of endodermal sinus tumors and so-called "embryonal" carcinoma of the ovary. Acta Pathol. Microbiol. Scand. 64 : 407, 1965. (21) Page 5 APRIL 21, 1974 - CASE NO , 4 ACCESSION NO. 20440 3, Pierce, G.B. and Abell, 11. R. : Embryonal carcinoma of the testis. Patho1, Ann. ~:27, 1970. 4. Huntington, R.W. and Bullock, W.K.: Endodermal sinus and other yolk sac tumors, a reapprisal. A~ta Pathol. Microbiol. Scand. 233:(Suppl) 26, 1972. 5. Huntington, R.W. and Bullock, W.K.: Yoll< sac tumors of the ovary, Cancer 25:1357, 1970. 6, Neubecker, R,D. and Breen, J.L.: Embryonal carcinoma of the ovary. Cancer 15 : 546, · 1962. 7, Wilkinson, E.J. et al. : Alpha-fetoprotein and endodermel sinus tumor of the ovary. Am. J. Obstet. Gynecol, 116:711, 1972. 8, Serov, S,F, and Scully, R,E.: Histologic typing of ovarian tumors. Geneva , 1973. World Health Organization. 9. Scully, R.E.: Recent progress in ovarian eancer. Rum. Pathol. 1:73, 1970. 10. Robboy, S. J, and Scully, R. E.: Ovarian teratoma with glial implants in the peritoneum. Hum, Pathol. 1:643,1970 Figure 1 Germ Cells ~ Seminoma - ~;ry~lnal Carcinoma t-- ~ Choriocarcinoma Endodermal Teratoma (Embryonic tissues) (Extraembryonic Sinus tumor tissues) (Extraembryonic tissues) I (22) APRIL 21 , 1974 • ~SE NO. 5 ACCESSION NO. 13317 MODERATOR'S DIAGNOSIS: Well differentiated adenocarcinoma of the cervix, cervical cell type. CLINICAL ABSTRACT: Thi.s is a 57 year old patient with vaginal discharge and intermittent spotting of blood. Examination revealed a polypoid lesion of the cervix and a cervical conization and n&c ·were done . The conization specimen sh~•ed the cervical stroma to be thickened by an infiltrating pinkish-yellow sticky tumor that surrounded the endocervical canal. The tumor extended to the margin of the cone. Following the conization a hysterectomy was performed. MICROSCOPIC DESCRIPTION: Sections of the tumor show large numbers of endocervical glandular structures present in the cervical stroma . These glandular structures have irregular shape, are crowded together in focal areas, appear to be infiltrating the cervical stroma, and are forming bizarre glandular configura tiona. In addition many of the glands have pointed, jagged angles and a lobster claw configuration can be noted in many of the tumor glands. High power examination indicates nuclear crowding, mild pleomorphism, and hyper chromacity. There is stratification of the nuclei and mitoses are numerous in all of the t umor gtanda. Budding and branching of tumor glands are prominent. DISCUSSION: This is an example of the well differentiated type of cervical cell adenocarcinoma of the cervix. Such adenocarcinomas can be very well differen tiated and can be difficult to separate from endocervical nyperplasia (1). At low power the most significant findings are tho glandular crowding, the irregular formation of the glands, and the pointed angl es and lobster claw like configurations. At higher power, the nuclei are almost always stratified, hyperchromatic, and,moat significantly, mitoses are found in large numbers (2,3). Mitoses are very unusual in benign cervical epithelium, and when they are present, well differentiated carcinoma must be considered. Because this type of adenocarcinoma is well differentiated it is often missed when care is not taken to examine the endocervical Blends at high magnification. Endocervical glandular hyperplasia may be found in a number of abnormal states including progestogen medication, presnancy and inflammation. Hyperplasia is characterized by crowding and increased numbers of glands as well as unusual configurations. However mitoses are very rare and the nuclei sh~~ only minor degrees of atypia and stratification. Also the bizarre shapes (23) Page 2 AERIL 21, 1974 - CASE NO. 5 hCCESSION NO. 13317 and angles of glands seen in carcinoma are not present in hyperplasia. Microglandular hyperplasia, as described in Case 3, may be confused with t Adenocarcinoma-in-situ occurs in the endocervix and the cellular atypia and the numbers of mitoses will be similar to that seen in carcinoma except there is no invasion. Proposed criteria for the diagnosis of adenocarcinoma in-situ of the cervix are as follows (4): 1. Anaplastic and neoplastic cells lining glands which are clearly endocervica1 in type. 2. Ttansitions between benign and malignant epithelium td.thin the glands which retain a normal or organoid pattern 3. Cells have the cytologic features of carcinoma including mitoses. 4. The supporting stroma-gland relationship is normal. 5. Invasion or infiltration by carcinoma cells or clusters of glands is not found. In summary, this is a case well differentiated adenocarcinoma of the cervix of the cervical cell type~ The importance of this type of lesion is that it can be so well differentiated as to be confused with endocervical gland hyperplasia and normal endocervical glands. It is very easy to miss this type of carcinoma if inspection of endocervical sections is casual and careful examination of the endocervix is required to make the diagnosis. The presence of mitoses, altered nuclear-cytoplasmic ratio, nuclear hyper chromatism and stratification are all features of carcinoma as is irregular shape of the glands. This type of carcinoma has also been designated as adenoma malignum, a term which should not be used (1) . (24) Page 3 APRIL 21, 1974 - CASE NO. 5 ACCESSION NO. 1g317 REFERENCES : 1. HcKe1vey, J.L, and Goodlin, R.R.: Adenoma malignum of the cervix. Cancer 16;549, 1963. 2, Abell, M.R.: Invasive carcinomas of the uterine cervix. In; No~ris , H.J. , Hertig, A.T, & Abell, M.R . Bds.: The Uterus, lAP Monog~aph 114. Baltimore 1973. The IUlliams & Willtins Company. p. '•37, 3. Abell, M,R, and Gosling, J,R.G. : Gland cell (adenocarcinoma) carcinoma of the uterine ce~vix . Am .J,Obstet.Gynecol, §1:729, 1962. 4. Weisbrot, I.M. et al.; Adenocarcinoma-in-situ of the uterine cervix, Cancer 29:1179, 1972. (25) APRIL 21, 1974 - CASE NO, 6 ACCESSION NO. 13900 MODERATOR'S DIAGNOSIS: Extrsmammsry Paset's disease of the vulva. CLINICAL ABSTRACT: The patient is a 60 year old who had s long history of vulvar pruritis which persisted despite treatment and became more intense, Finally white plaques developed on the vulvar skin and these became confluent forming a horseshoe-shaped area with the clitoris in the central portion. A vulvectomy was performed and the specimen showed irregular white plaques extending from the prepuce ~f the clitoris on to the labia majora in a zone measuring 35 x 25 mm . in greatest dimensions. The lesion was re-excised following the inital excision and the patient was free of disease for eight years. In 1972, plaques again developed and a biopsy showed Paget's disease. She was treated conservatively for a year and the lesion spread from the pubis to the anus. ~aCROSCOPIC DESCRIPTION: The epithelium is focally hyperplastic with mild hyperkeratosis in many areas. l Extramammary Paget's disease of the vulva (1,2.3) occurs in older indi vlduols at on overage age- of sixty, It is rare under the age of fifty and practically unknown under the age of thirty, Page t's disease of the vulva represents one par t of the spectrum of ano-cenital Paget's, which may also involve the perineum, perianal region, the thighs, end the male genitalia. There are no kn~~n causative factors. Clinically, the lesions are character istically reddened, eczematoid, elevated, edematous, and indurated but may (26) APRIL 21, 1974 - CASE NO, 6 ACCESSION NO, 139eO be plaque-like and ~Thite as in this case, Thus , Paget's disease must be considered in the differenti al diagnosis of so- called l eukoplakia. The lesions are frequently ulcerated with oozing, crusting, and scalin(l. Pruritis is universal ~nd severe. The duration of the disease is usually long and the lesions are often initially i nterpr eted clinically as dermatitis, vul var dystrophy, hyperkeratosis, or other inflammatory diseases. Paget's disease is just one of the many entities which emphasize the necessity of early biopsy as a part of the diacnoatic procedures for patients with vulvar skin lesions. The histogenesis of Paget's disease is controversial but recent studies indicat e origin in the epidermis (1) . Observations '~hich support intra epidermal origin are the following: A. The lesion i nvariably occurs first in t he epidermis and dermal involvement is secondary, Adnexal involvement alone is not seen. B. !~hen invasive carcinoma is present, the invasion occurs from the epidermis into t he dermis, not from the dermis into the epidermis. c. Ultrastructural studies support, but do not prove, en epithelial crigin. Ultrastr ucturally, ther e are deemoeomea be t ween P~get's cells and squamous cells, and beo·Teen Paget 1 s cells and Paget' s cells (l•) . Ultrastructural studies suggest an in-situ transformation of squ.emous epithelial cells to Paget's cells. The evidence also supports a multifocal origin along Hide areas of the epidermis and >~ithin eccrine ducts. Other theories of origin have also been suggested, These include intra-epi thelial spread-of an adenocarcinoma from underlying sweat elands. There is little support for this theory. It has also been suggested that Paget's disease i s a f orm of melanoma; however, melanin i s not present in the tumor cells and desmosomes are not seen between melanocyte& as are present bco~een Paget' s cells. Paget's cells may contain melanosomea, but so may squamous cells (4). I interpret Paget 1 s disease as adenocarcinoma-in- situ involving tho epidermis, whether it occurs in the breast or in the ano-gcnital region. In vulvar Paget 's disease, about one-sixth of the patients will have under l ying invasive adenocarcinoma. The incidence of invasive carcinoma associated with Paget's disease varies with the site, with 10~ incidence in the breast, and about 80% incidence in perianal Paget's disease (1 , 3). The course of Paget's disease is prolonged and the lesion usuall y spreads slowly. BO«ever, until invasion of the dermis occurs, the lesion is localized (27) Page 3 t.PRIL 2l, 1974 - CASE NO. 6 ACCESSION NO. 13900 to the epidermis and does not metastasize. If invasive carcLnome is present, it often can be detected clinically because of ulceration or the presence of a mass. Patients with Paget' s disease should have multiple biopsies to rulo out invasion and to determine margins. At the time of excision, frozen sections of the surgical margins ia often advised because Paget's cells can be found outside what appears to be the clinical marains of the lesion. Recommended therapy is complete local excision es long as invasion has not occurred. When invasion is present radical vulvectomy with node dissection is the treatment of choice. Thirty percent of the patients with Paget's disease have maliznancies in other organs including rectal, anal, and sueat ~l and carcinomas (3). The differential diagnosis in Paget's disease must always include malignant melanoma (5). The nodular form of malignant melanoma is usualty little trouble clinically or histologically. H~~ever , superficial spreading malignant melanoma clinically may be erythematous and weeping and thus some uhat resemble Paget's disease. Histologically, the so-celled "Pagetoid" cells in superficial spreading malienant melanoma can very closely resemble true Paget's cell (6) . HOI·Iever , the tumor cells in malignant melanoma do not involve t he sweat s l ands as Page t's disease frequently does, melanoma cells are not mucin positive as are Paget's cells, and most importantly, melanoma cells do not form glandular acini containing mucin. In our experience the PAS with diastase is the most reliable stain to determine the presence of mucin within tumor cells although Helwig bas advocated use of the aldehyde fuchsin reaction because melanoma cells may occasionally contain small amounts of PAS diastase resistant materiel (3). The combination of fllond formation by tumor cells, eccrine sweat eland involvement, and a positi ve mucin stain, allow separation of Paget's disease fr om superficial spreading malignant melanoma (1). Anot her entity which may be confused •~ith Paget's disease is Bowen's disease (7) . Althouzh this entity usually causes no trouble B~·1enoid cells may have clear cytoplasm but such cells are mucin negative. The presence of mucin as •~e ll as the involvement of the sweat &lands end glandular formation by tumor cells, serves to separate Paget' s disease from Bowen's disease. RBPERENCES : l, Koss, L.G. et ol. : Paset's disease of the vulva. Report of 10 cases, Obstet. & Gynecol. 31:513, 1968 . 2. Penn, ~t . E., '! 3. l!cb1ig, E.G. and Graham, J .H. : Anogenitsl (extra-mammary) Paget's disease, Cancer ]!:387, 1963. (28) Page 4 /1PRIL 21, 1974 - CASE NO. 6 ACCESSION NO. 13900 4. Sagebiel, R.W . : Ultrastructua1 observation-On epidermal cell in Paget's disease of the breast. Am. J. Path. 21:49, 1969. 5. Fenn, M.B. and Abell, M. R.: Melanomas of vulva and vagina. Obstet. & Gynecol. 41:902, 1973. 6. Clark, H,H. et ol. : The histoeenesis and histologic behavior of primary malignant melanomas of t11e skin, Cancer Res. ~:705, 1969, 7. Abell, M. R. and Gosling, J . R.G.: lntraepithelial and tnfiltrating carcinomas of the vulva, Bowen's type. Cancer 14:318, 1961. (29) APRIL 21, 1974 - CASE NO . 7 ACCESSION NO • 12 799 i10DERATOR'S DIAGNOSIS : Epithelioid leiomyoma present in space s consistent 11ith intravenous leiomyomatosis CLINICAL ABSTRACT: This patient is a 36 year old female Hho developed a pelvic mass thought to be a leiomyoma silt years prior to hysterectomy. At hysterectomy, the uterus \/eighed 1200 grams and included a pedunculated mass, 13 ems. in diameter. In addition to the pedunculated tumor, lntich had the gross appearance of a leiomyoma, there Here multiple intramural leiomyomas, the largest measuring 6 .5 ems. in diameter. The latter had a bulging cut surface composed of closely oriented multiface ted nodules of homogeneous tissue resembling kernels of corn. These were separated by slit- like spaces. MICROSCOPIC DESCRIPTIOH: This tumor is composed of cords, clusters and sheets of cells ui.th vesicular somewhat irregular nuclei. There is extensive hyal inization present throughout the tumor and many of t he tumor cells are completely surrounded by hyaline. Vessels are present in the mass but are not s trikingly thicl< Halled. The tumor is some1~hat more cellular at the periphery, and in these areas, the tumor cells have an epithelioid appearance ~lith striking clearing of the cytoplasm. At the edge of the section there is a small fragment of normal myometrium l~hich appears to be lined by elongate endo thelial- like cella suggesting that the mass is present in a vascu1 ...,. space. The tumor cells do not contain mitoses. There is only minimal pleomorphiem and giant cells are not found . DISCUSSIOl~: I cons ider this tumor to be of smooth muscle origin and to belong to the group of smooth muscle tumors \mo~m as "bizarre" leiomyoma&. These t·tere first described by Stout under the title "leiomyoblastomas of the stomach" and several varieties have since boon deecribed in the stomach, and other sites, including the uterus (1,2,3). The classic leiomyoblastoms is a cellular tumor in which the tumor cells have cytoplasmic clearing around a central nucleus r esulting in a unique "fried .egg" appearance. In addition to the leiomyoblastoma type of bizarre leiomyoma, we have encountered clear cell leiomyomas in the uterus and lesions such as this one, t-7hicb have been designated as "epithelioid cell" leiomyomas because of the epithelial-like appearance of the t umor cells (2,3) . The epithelioid type of leiomyoma is characterized by cells having varying degrees of cytoplasmic clearing tohich are arranged in a linear and often epithelial- like arrangement. The epithelioid leiomyomas always contain extensive amounts of hyaline . The importance of recognizing these bizarre leiomyomas is to avoid mistaking them for either leiomyosarcoma or other malignancies. I n this case, the absence (30) Page 2 APRIL 21, 1974 - CASE 50. 7 ACCESSION UO . 12799 of mitosis eliminates the possibility of leiomyosarcoma. Because of the apparent presence of tumor tissue in vascular spaces, the possibility of endolymphatic stromal myosis must be considered. However, the tumor cells do not resemble endometrial stromal cells. Intravenous leiomyomatosis is distinctly a consideration. Certainly, the gross description 1·1ould fit that entity and the sections sho1·7 the lesion to be present in 11hat I thinlc is a vascular space although this is not definitive in the material available to us for examination. Intravenous leiomyomatosis is a rare condition in which benign smooth muscle is present in vascular spaces (4,5) . It occurs in older patients, usually in their fifties or sixties . There are no specific symptoms and the patients are almost ah1ays operated on because of an enlarged uterus thought to be dufl to leiomyomas . The lesion is seen grossly as intravascular tumor masses which can usually be easily pulled out of the vessels. In about half of the cases the tumor has extended into the veins of the broad ligament or beyond at the time of surgery. The lesion is benign in spite of the vascular invasion and, in most instances, even if tumor is left behind in vessels, nothing further happens. In two instances, however, intravenous masses of smooth muscle extended up the vena cava and caused the death of the patient. (5). This is an extremely rare event and in all other instances, the lesion has been perfectly harmless. Histologically, the material inside the vessels is benign smooth muscle t~ithout evidence of mitoses or significant atypism. Claracteristically there is extensive hyalinization of the smooth muscle and thict~ 1·1alled blood vessels are frequently prominent. At lo~' p01ier, the most distinctive feature histologically is the proliferation of smooth muscle tumor tissue in vascular spaces. The pathogenesis is unl REFERE!ICBS: 1. Stout, A. P.: Bizarre smooth muscle tumors of the stomach. Cancer 15: 400, 1962. 2. R)"·7lin, A. H., et al: Clear cell leiomyoma of the uterus, Cancer £: 100, 1964, 3. Kempson, R. L. : Sarcomas and related lesions. In: Iqorris, H. J., Hertig, A. T. and Abell, M. R. Eds . The Uterus, lAP monograph /114. Baltimore, 1973. The flilliams and liilkins Co. Page 29S . 4. Harper, R. S. and Scully, R. E.: Intravenous leiomyomatosis of the uterus, Obstet, and Gynecol. 18:519, 1961 . 5. Edwards, D. L. and Peacoclc, J. F.: Intravenous leiomyomatosis of the uterus. Obstet. Gynecol. 27:176, 1966. (31) APRIL 21, 1974 - CASE NO . 3 ACCESS ION !10. 12903 / l«lDERATOR ' S DIAGNOSIS: l>lalignant mixed Hulllerian tumor, heterologous type. CLINICAL ABSTRACT: The patient is an 83 year old female l·lho had radium therapy in 1955 for carcinoma of the cervix. In 1963, she developed intestinal obstruction secondary to metastatic carcinoma. At surgery a huge mass filled the pelvis and many of the lymph nodes contained metastatic tumor. She died following a colostomy. At autopsy the pelvic mass l·las noted to be primar ily an intrauterine tumor ~1hich l·/as polypoid and zray white "ith areas of brotm and red necrosis. The tumor lias 6 em. in leng th aod 3.4 ems. in diameter aod had gro~m through the uterine Hall and obliterated both adnexal structures. MICROSCOPIC DESCRIPTION: This tumor presents several different histologic patterns. In some areas there is adenocarcinoma present '~ith ~1ell formed gland spaces lined by neoplastic cells containing numerous mitoses. In other areas, the tumor appears to be formed by undifferentiated mesenchyme while in other areas there is malignant stroma suggesting smooth muscle differentiation. Yet other areas resemble neoplastic endometrial stroma and in these latter areas, islands of squamous epithelium can also be found. The stroma is definitely sarcomatous and the pleomorphic tumor cells contain numerous mitoses. As mentioned above, the epithelial elements also demonstrate the changes of carcinoma. In areas, there is cartilaginous differentiation and the cartilage has the histologic appearance of chondrosarcoma. DISCUSSIO!~: The differential diagnosis of malignant mixed l~llerian tumors must ah~ays include undifferentiated and poorly differentiated carcinomas since some carcinomas may be so poorly differentiated as to resemble sarcoma. This is particularly true in those carcinomas lmich have a basophilic hyalinized stroma somm~hat resembling cartilage. Before mat~ing a diagnosis of malignant mixed l1ullerian tumors, one should be sure that there is a sarcomatous element present in the tumor. In this tumor, l: think there is little doubt that leiomyosarcoma, stromal sarcoma and chondrosarcoma are present. Mixed sarcomas must also be included in the differential diagnosis. Ho~1ever, there is definitely carcinoma present in this tumor, thus indicating a malignant mixed Mullerian tumor. Malicnant mixed t1ullerian tumors must all~ays be differentiated from teratomas. This is particularly true in the ovary where mixed Huller ian tumors may also occur. As poin ted out by Dehner (32) Page 2 APRIL 21, 1974 • CASE NO. 8 ACCESSION NO. 12903 and Norris, teratomas are seen in a younger age group. There is a broader range of tissue differentiation in teratoma, neural tissue and germ cell elements are found in teratomas, and the stror•a in mixed Hullerian tumors is sarcomatous rather than irnlllature or adult as seen in teratomas (1). Nalignant mixed Hullerien tumors represent one of the more common types of uterine sarcomas and, as mentioned in the discussion of case 2, are designated as heterologous or hornologous depending upon the differentiation of the sarcomatous tissue present " (2,~). Other terms used are carcinoma sarcoma and mixed mesodermal tumor to designate the homologous and he'er ologous tumors respectively (4,5). ~!alignant mixed Mullerian tumors represent approximately 1% of all uterine malignancies and arc equal in frequency to l eiomyosarcoma in most of the larger series. The tumor m~inly affects older patients and it is rare under the age of 30. Most patients are in their SO's and 60's. Abnormal vaginal bleeding is a universal symptom and the uterus is often enlarged at the time of diagnosis. The tumor may protrude from the cervical os and at times can be botryoid. Malignant mixed Mullerian tumors should not be designated as sarcoma botryoides however, since that term implies embryonal rhabdomyosarcoma. Grossly, malignant mixed Mullerian tumors are usually polypoid fungating hemorrhagic necrotic masses often involving large portions of the uterus. They frequently have invaded the myometrium deeply at the time of diagnosis. The treatment is hysterectomy. Survival depends on the extent of the tumor, the depth of myometrial invasion and, to a lesser extent, on the type of tumor tissue differentiation (6). Patients who have survived are almost invariably those whose tumors were small with only superficial or no invasion of the myometrium. Hhen the heterologous elements are skeletal muscle and bone, survival is very poor; it is somewhat better when heterologous element is cartilage, Patients with homologous tumors have been reported to have o better survival than those with heterologous tumors (4,5). The histogenesis of mal ignant mixed Mullerian tumors is unknown but they are thought to arise from the end Page 3 APRIL 21, 1974 - CASE NO. 8 ACCESSION NO, 12903 mixed Mullerian tumor must be considered. Curettage and biopsy material will not be representative if only the carcinomatous element or only the sarcomatous tissue is present in the biopsy. Malignant mixed Mullerian tumor s also occur in the fallopian tubes end ovaries where they are considered to arise from the coelomic (surface) epithelium (8,9). They have a similar prognosis in these locations. 'l\1elve to fifteen percent of patients with malignant mixed Hullerian tumors have had prior radiation therapy to the pelvis. A history of prior radiation is rarely elicited in patients with other types of sarcoma (10). REFBRNCBS : l. Dehner, L. P., Norris, H. J. and Taylor, H. B.: Carcinosarcomas a~d mixed mesodermal tumors of tha ovary. Cancer ~:207, 1971. 7. Kempson, R. L: Sarcomas and related lesions. In: Norris, H. J., Hertig, A. and Abe ll, M. R. Eds. The Uterus, LAP monograph Dl 4 . Baltimore 1973. The Hilliams and Hilkins Co. p. 293. 3. Kempson, R. L. end Bari, 1'1: Uterine sarcomas. Hum. Path, .!:331, 1970, l,. Norris, H. J, et al: Mesenchymal tumors of the uterus. II - A clinical and patholoeic study of 31 mixed mesodermal tumors. Obstet, & Gynecol. 28:57, 1966, 5. Norris, H. J. and Taylor, H. B: Mesenchyma l tumors of the uterus. III - t. clinical and pathologic study of 31 carcinosarcomas. Cancer 19: 1459, 1966. 6. Schaepman-Van Geuns, E. J: Mixed tumors and carcinosarcomas of the uterus evaluated 5 years after treatment. Cancer 25:72, 1970. 7. Silverberg, S. G.: Halignant mixed mesoderllllll tumor of the uterus: an ultrastructural study. Am . J. Obstet. Gynecol. 110:702, 1971 . 8. Hu, J. P. et a1: Nalignent mixed Hullerian tumor of tlhe uterine tube. Obstet. & Gynecol. 41:707, 1972. 9. Fenn, ll. E. and Abell, •t. R.: Carcinosarcoma of the ovary. Am . J. Obstet. & Gyneco1. 110:1066, 1971. 10. Norris, H. J. and Taylor, H. B.: Post irradiation sarcomas of the uterus. Obstet. and Gynceol. 26:689, 1965. (34) APRIL 21, 1974 - CASE NO. 9 ACCESSION NO. 12998 MODERATOR'S DIAGNOSIS: Syncyti.al endometriti.s (implantation site}. CLINIChL ABSTRACT: This 24 year old female was admitted in 1963 for r emove 1 of a left ovarian cyst which had increased in size since it had been discovered one year previously. She l·las gravida 1, para 1 and had delivere.d an infant in 1960. In 1961, a right ovarian cyst had been removed bo,lt the type of cyst i s unknown. She had been receiving cyclic hormone therapy. Pelvic examina tion revealed a movable non-tender G em. mass in the left adnexal reeion and a hysterectomy snd left salpinzo-oophorectomy uere performed. Grossly, near the left tube, there was a 0. 4 em. poorly delineated nodule which bulged from the serosal surface of the uterus. There were not other myometrial lesions. The endomet rial cavity ttas enlarged by D lobulated, yellowis h tan tumor that measured 4 x 2.5 x 1.5 em. This tumor was attached along the posterosuperior wall. The mass uas partially cystic, friable, and blended into the under lyin& myCKnetrium . The left ovary ~188 multiloculated and cystic. The sections in this case are apparently taloon from the endometrial mass . MICROSCOPIC DESCRIPTION: The endometrium in t he areas from which the sections '~ere taken shm~s a florid decidual reaction. Overlying the decidua are round cystic spaces, ~1hich at low pmoe:; resemble chorionic villi, but arc noted to be surrounded by decidua at high po.1er, and represent dilated endome trial glands demonstrat ins so-called secretory exhaustion. ~lithin the decidua and i n the myometrium are large numbers of cells with abundant eosinophilic cytoplasm and atypical nuclei. Many of these cells are multinucleated and they infiltrate the •1alls of blood vessels and interdigitate amon::; muscle fibers in the upper portion of the myometrium. Abnormal mitoses are occasionall y noted. There is focal, and rather minimal, chronic inflmnmation \lithout evidence of hemorrhage or necrosis. The muscle fibers surrounded by the cells appear to be viable and occasional muscle giant cell forms are also present. The • remainder of the myometrium is not remarkable. DISCUSSION: Although 1t is unusual to find syncyt ial metritis presenting as a gross mass in a patient Hho has not been ltn01m to be preenant, I thin!< this is syncytial metritis and represents a missed abortion. Closer questioning of the patient mi::;ht have revealed a history of abnormal uterine bleeding in the recent past. The main consideration in the differential diagnosis is, of course, choriocarcinoma. Choriocarcinoma is inevitably composed of both cyto and syncytial trophoblast& with the syncytial trophobl asts usually (35) Page 2 hPRIL 21, 1974 - CASE NO, 9 ACCESSI ON NO . 12998 arranged over and around the clusters of cytotrophoblast as a cap (1). In addition, choriocarcinoma is al1~ays associated with hemorrhage and necrosis whi ch is not found in these sections (2), The degree of cellular atypia and the presence of mitoses and abnormal mitoses are not particularly hel pful since they can be found in both syncytial metritis an Choriocarcinoma can be very diffi cult to diagnose from curettings and atypical trophoblastic proli feration in pregnancies can be troubl esome(3,5). It is probable that choriocarci-noma cann<>t be diagnoccd histoloeically from curettings in more than one third of the cases . However, the combination of clinical pattern, chorionic gonadotropin titers and tlle bistolocy often all~• a proper diagnosis. In some instances accur ate classification of the trophoblastic process is not possible and a diagnosis of trophoblastic disease must be made . Invasion of the myometrium by the trophoblast is a char acterist ic of all pregnancies (6). The decree of invasion is variable but cea be extensive snd trophoblasts can invade rather deeply into t he myometrium nnd into vessel (36) Page 3 APRIL 21, 1974 - CASE NO. 9 ACCESSION NO. 12998 walls . The invasive cells are both syncytial and cytotrophoblast& and differentiation of these cell types is •ometimes difficu~t when they are in the uterine wa ll (6). It is often difficult to separate trophoblasts from atypical decidual cells and muscle giant cells. In some instances, the trophoblaats may persist at the implantation site for a long period of time after a pregnancy as in this case, and careful separation from mole and choriocarcinoma is imperat ive. REFERENCES : 1. Park, W.W.: Choriocarcinoma; a study of its pathol ogy. Pbil a. 1971, F . A. Davia. Co. 2. Elston, C.W.: Cellular reaction to choriocarcinomas, J . Patbol, 97:261, 1969. 3. • Elston, C. ~1 . and Ba gs hs~<~e, K. D. The diagnosis of trophoblastic tumors from uterine curettings . J . Clin. Patbol. 25:111, 1972. 4. Isbizuka, N. et al.: Gonadotropin and steroid hormone excretion in trophoblastic neoplasia. Obstet. & Gynecol. 42:1, 1973. 5. Jequier, A.M. and Winterton, W.R.: Diagnostic pr9blems of trophoblastic disease in women aged 50 or more. Obstet. & Gynecol. 42:378, 1973. 6. Driscoll, S.C.: Placental-uterine inter-relationships. In: Norris, H.J., Hertig, A., Abell, M. R. Eds. The Uterus IAP monograph #14. Baltimore 1973. The Williams and lJilkins Co. p.213 (37) APRIL 21, 1974 - CASE NO, 10 ACCESSION NO . 12802 MODERATOR'S DIAGNOSIS: Malignant lymphoma, unclassified (?Burkitt's lymphoma, ? poorly differentiated lymphocytic lymphoma diffuse) CLINICAL ABSTRACT: This 15 year old female noted lower abdominal pain and abdominal enlargement one week prior to admission. She had had a normal menstrual period 10 days prior to admission. Physical examination revealed a very hard tender mass e.xtending from the symphysis to the umbilicus with a second mass near the epigastric areo. Her white count was 12,300 with 63 segs and 25 lymphocytes. No mention of a bone marrow examination is made. An appendectomy and bilateral salping-oophorectomy were performed. The left ovary was replaced by 630 gms. mass mea suring 15 x 12 x 8 em . This was solid, soft, smooth and light tan with a few cystic mucoid areas. The right ovary weighed 800 gms. and was similar to the left one. There waa a small nodule on the serosa of the fallopian tube and one in the mesosalpinx. MICROSCOPIC DESCRIPTION: Unfortunately, the tissue in this case is not ideally preserved making interpretation diffult. The tumor is composed of monotonous masses of lym phoid like cells which have irregularly shaped nuclei and are of variable size. ~titoses are present and the cells appear to have a small amount of amphophilic cytoplasm. Necrosis is prominent. At low power in some areas of the tumor, histiocytes are present surrounded by a space resulting in the so-called starry sky appearance. A MGP stein was negative as were the ASD chloracetate esterase stain and PAS. Cytoplasmic vacuoles are not noted. DISCUSSION: The differential diagnosis in this case ~1ould include lymphoma, leukemia and the group of small round cell malignant tumors which occur in childhood, namely neur oblastoma, Ewing's tumor , embryonal rhabdomyosarcoma and Wilm's tumor. I have interpreted this case as a malignant lymphoma and a primary consideration is, of course, Burkitt' s lymphoma. Burkitt's lymphoma is a form of undifferentiated malignant lymphoma for which clinicopathologic criteria were established in 1969 (1). According to the Rappaport classifi cation, Burkitt' s tumor Hould fall into the category of undifferentiated diffuse malignant lymphoma and under the new classification of Dorfman, Burkitt's lymphoma would be included under the lymphomas and diagnosed as such (2), Criteria for the diagnosis of Burkitt's lymphoma include cells with little variation in size end shape, increased numbers of mitoses, and starry sky pattern ,.ith nuclear debris in the cytoplasm of the histiocytes. (38) Page 2 APRIL 21 , 1974 - CASE NO. 10 ACCESSION NO. 12802 The tumor cells usually have a narrow rim of amphophilic cytoplasm and cytoplasmic vacuoles are common. These latter can be best seen under oil immersion. The nuclei contain coarse chromatin, are uniform in size, and have prominent, and often multiple nucleorL Rapid and thorough fixation ore necessary to bring out the uniformity of the cells and the cytoplasmic characteristics. In addition, imprint s are very helpful in malting the diagnosis of Burkitt's l ymphoma accurately since the Romanofsky stain brings out cytologic details, fat stains will demonstrate the lipid in the vacuoles, and cytoplasmic pyrinophilia con be demonstrated. The tumor cells are MGP positive, PAS and esterase nesative (1,3) . In this case, I think the cells are too irregular in size and shape for this tumor to be diagnosed unequivocally as Burkitt's tumor although sub optimal f i xation moy be re ~ponsible f or the cellular i r regularity. Addition ally, the HGP is negative ond it should be positive in Burki tt 'a tumor . Poorly fixed cells will lose pyrinophilia and this may have been the case here. This emphasizes the necessity for imprints and rapid fixation. I would consider this tumor to be mal ignant lymphoma which I cannot further classify. It could be a Burkitt's tumor in which the tissue has been poorly fixed resulting in loss of cellular uniformity ond cytoplasmic pyrinophilia. lt could al so be a poorl y differentiated lymphocytic lymphoma of the diffuse type . The "starry sky" pat tern is not s pecific for Burkitt's and can be found in a number of other l ymphomas and l eukemias. I do not think t his is histiocytic lymphoma since the cells in that tumor should have abundant cytoplasm and lar&e cytoplasmic vacuoles. The cytoplasmic vacuoles in histiocytes are fat negative and there is variable MGP staining. Nodular poorly differentiated lymphocytic lymphoma cells are irregular and hove so-called nuclear clefts or indentations which are not seen in this case. The HGP and PAS stains ar e also negative. Leukemia should be considered in the differential diagnosis. In l ympho blastic leukemia, the nuclei sre somewhat smaller than hi.stiocytes, have delicate chromatin and somewhat resemble the cells seen in this tumor. Therefore, a bone mor•oo• examination would be indicated for this patient. Lymphoblastic leukemia cells hove weak to no NGP staining but do contain PAS positive diastase r Gsistance sensitive granules. These wera not found in this case and therefore, I doubt that this is lymphoblastic leukemia. I also doubt that this i s myclobl~stic leukemia since eosinophilic myclocytes are not present. The ASD chloracetate esterase was negative whereas it should be positive in my~locytes, and PAS positive granules were not found. There is a group of neoplasms occurrina primarily in childhood which should also be considered in the differential diacnosis . These include neuroblastoma, EwinG's tumor, embryonal r habdomyosarcoma and Wilm'a tumor. (39) Page 3 APRIL 21, 197l, • CASE NO. 10 ACCESSI ON NO. 12802 Rosettes are not found in this tumor and I do not think this is neuroblastoma. However, catecholamine deter minations shoul d be done since urinary catecho lamines will be elevated in neuroblastoma. A diagnosis of neuroblastoma can often be made quickly by el ectron microscopy or tissue culture. In Ewing's sarcoma the tumor cells usually contain clycogen and the PAS stains should be positive. Embryonal rhabdomyosarcoma has a myxoid stroma '~hich is not present in this tumor. llilm' s tumor may have evidence of tubular differentiation. It is rare for lymphomas to present primarily in the ovary. Rm~ever, one of the features of Burkitt's tumor is involvement of the gonads in females (4,5). It characteristically occurs in children snd young adults and ordinarily there are no tumor cells in the blood and a frankly leukemic blood picture is almost never present. Extranodal involvement is prominent in Burkitt's tumor, particul arly in the retroperitoneal soft tissue, abdominal viscera, gonards and other endocrine orcains. The spleen is either minimally or not involved. Frequently there is sparing of the peripheral lymph nodes and the retroperitoneal lymph node may be spared even in the presence of massive involvement of the retroperitoneal soft tissue. Hediastinal lymph node invol vement is very rare (6, 7) . The clinical presentation in this case is compatible with Burkitt's tumor, but definitive histopatholos ic criteria are not present as noted above, Other typee of lymphoma may rarely appear first in the gonads (8) . Particularly important is the occurrence of histiocytic lymphoma in the testicle. The prognosis for pati.ents presenting 'dth gonadal lymphoma has been poor. REFERENCES: 1. Berard, C., e t al. : Histopathological definition of Burkitt's tumor. W. H.O. Bull. 40, 601, 1969. 2. Dorfman, R.F.: Pr cposed classification of non-Hodgkin's lymphoma. To be ?Ublished in Lancet. 3. Dorfman, R.F, : Diagnosis of Burkitt's tumor in the United States. Cancer !h:S63, 1968. 4. Wrinht, D.H.: Burkitt's tumor and childhood lymphosarcoma. Clin. Pediat. §.:116, 1967. 5. Finkle, H.I and Goldman, R.L.: Burkitt's lymphoma, gynecologic considera tions, Obs t et. & Gyneeol. 43:281, 1973. (40) Page 4 APRIL 21, 1974 - CASE NO. 10 ACCESSION NO . 12802 6, Burkitt, D.P • . and Wright, O,H.: Burkitt's lymphoma. London 1970. E. & S, Livingstone. 7, Cohen, M.H. et al,: Burkitt's tumor in the United States. Cancer~: 1259, 1969. 8.. t~oodruff, J . D. et al.: Lymphoma of the ovary. A study of 35 cases, Am . J, Obatet. & Gynecol.·85:912, 1963. (41) f1PR1L 21, 1974 - CIISI!! NO . 11 ACCESSION NO. 11497 ~!ODERI\TOR 'S DI/IGNOSIS: Endometrial stromal sarcoma CLINICAL ABSTRI\CT: This 51 year old fema le had a lon(l history of dysmenorrhea with almost continuous vaginal bleeding for three months prior to admission to the hospital. Physical examination reveal ed vaginal bleeding and a polyp protruding from the cervical ·os. A D&C was done and large amount of yella<1 polypoid smooth material t~as obtained. Follcn DISCUSSION: Endometrial stromal neoplasms may be divided into three types as noted in Table 4 (1,2) . These are stromal nodules, endolymphatic stromal myosis and stromal sarcoma. The criteria used to seporate these three entities includo pushing versus infiltrating margins and the number of mitoses per 10 hifl h powe r fields. Tumors with pushing margins are considered stromal nodules while those ~lith infiltrating margins are considered to be endol ym phatic s tromal myosis or stromal sarcoma. Stromal sarcomas are those infiltrating stromal neoplasms with more than 10 mitoses per 10 high power fields ~•bile endcljmphotic myosis is an infiltratine tumor ~lith less than 10 mitoses/10 HPF. Endometrial stromal tumors moy be pr esent in vascular spaces but this is particularly frequent in endolymphatic stromal myosis. Pleomorphism of tumor cells is of little value in separating stromal neoplasms . The same precautions and care to obtain representative and sufficient sections for mitotic counts DS noted for smoot h musc le tumors should be used for the (42) Page 2 hPRIL 21, 1974 - Cf,SE NO . 11 hCCESSI ON NO , 11497 stromal tumors . Infiltrating stromal tumors of the uterus are usually found in older patients bu t we have encounter ed them in chil dren (3) . Almost, invariably the patients present with abnormal vaginal bleeding and frequently there is a mass protrudins from the cervix. Grossly stromal tumors are yellow ~1hite to gr ay with frequent areas of necrosis. Endolymphatic stromal myosis may present as worm like masses in vascular spaces which can be seen zrossly. Sometimes these masses may extend beyon~ the uterus into the broad ligament and other structures. Endometrial stromal sarcomas frequently bulge into the endometrial cavity and infiltrate the myometrium widely. Endometrial stromal tumors are composed of rather uniform cells with scant cytoplasm. Bndolymphatic stromal myosis has tt;o rather distinct forms. In the first of these, mitoses ore very sparse or not found at all. The stromal is hyalinized and thick walled blood vessels are frequently present in the tumor masses . This form of the neoplasm is almost always confined to the uterus with involvement of vascular spaces being common. In the second form, mitoses are more easily found but do not exceed 10/10 HPP . Hyalinization is l ess marked, vascular involvement is not sb1ays present and thick walled blood vessels are inconspicuous . The prognosis for endolymphatic stromal myosis is directly related to the presence or absence of tumor Otttside of the uterus. I t is very unusual for lesions which do not extend beyond the uterus to recur but recurrence is frequent when tumor extends outside the ut erus. Recurrences of endolymphatic stromal myosis is almost always locally in the pelvis. Al though me tastases may occur, they usually do so only after local recurrence. Recrudescence of the tumor may occur long periods after the uterus has been removed; up to 25 and 30 years in some instances. There is some tendency for tumors with more mitoses to have a highEr recurrence rate. Endometrial stromal sarcoma is a much more sGgress ~ve tumor and metastases are more common. The overall survival in stromal sarcoma is be tween 30 and 407.. Both endol ymphatic stromal myosis and stromal sarcoma may arise outside the uterus, most commonly in the fallopian tube, the peritoneum or in the b~1el (4,5). Often, but not always, these extrauterine tumors are associated 1~ith endometriosis. The differential discrnosis of endometrial stromal tumors should include lymphoma and leukemia, particularl y histiocytic lymphoma. The sheet l ike arran3ement of the tumor cells, the vascular involvement and the cohesiveness of the cells plus the lack of the distinct cytoplasmic borders in stromal tumors usually help to rule out the possibility of lymphoma or leukemia . Nucleoli are prominent in histiocytic lymphoma snd are unusual i n ooot stromal tumors. However, at times the differentiation bet1·1een lymphoma and stromal (43) Page 3 APRIL 21, 1974 - CASE NO, 11 ACCESSION NO, 11497 sarcoma can be extremely difficult. Undifferentiated endometrial carcinoma can also resemble stromal sarcoma. Glandular structures can be found in stromal tumors as well as in carcinoma. ~~ever, the glands and tumor cells in carcinoma are more pleomorphic than in stromal sarcoma. A reticulin stain can be very useful. Since carcinoma is characterized by large clusters of cells surrounded by reticulum whereas in stromal sarcoma single cells or at most, very small groups of cells, are surrounded by reticulum fibers, Intravenous leiomyomatosis involves the uterine vessels in the same manner as endolymphatic stromal myosis and differentiation depends upon the demon stration of smooth muscle in the former condition. The tumor cells in leiomyomotosis are spindled and stain as smooth muscle with the trichrome stain. Malignant mixed Mullerian tumors may contain stroma l sarcoma as one of the sarcomatous elements and can cause confusion 1~ith stromal sarcoma. ~fuen glands occur in stromal sarcoma they ore not histologically malignant as they are in malignant mixed Hullerien tumors. Stromal sarcomas have often been confused with hemangiopericytoma. H~ever, stromal sarcomas do not have the vascular pattern of that tumor and do not shOI't the tuft and t~eave pattern which ia characteristic of pericytoma. Hemangiopericytoma of the uterus does occur but it is very rare and usually is easily distinguished from the stromal neoplasms (6), Metastatic undifferentiated carcin~ can also resemble the infiltrating stromal tumors but the carcinoma cells are usually more pleo morphic than the cells in the stromal sarcoma. REFERENCES: 1. Norris, H.J. and Taylor, H.B.: A clinical and pathological study of 53 endometrial stromal tumors. Cancer ~:755, 1966. 2. Kempson, R.L.: Uterine Sarcomas. In: Norris, H.J., Hertig, A. and Abell, M.R.: The Uterus, lAP monograph 114. Baltimore, 1973. The l~illioms and Wilkins Co. p. 298. 3, Kempson, R.L, and Bari, 1~ .: Uterine Sarcomas. Hum. Psthol. 1:331, 1970. l>. Palladino, V.s. & Trousdell, M, -: Extra-uterine Huller ian tumors. Cancer 23:1413, 1964, 5. Gerber, H.A , and Tol 6. Silverberg, S.C. et al.: Hemangiopericytoma of the uterus; an ultra· structural study, Am . J . Obstet, & Gynecol. l!Q:397, 1971, (44) Pace 4 APRIL 21, 1974 • CASE NO, 11 ACCESSION NO , 11497 Table 6 Pathologic Characteristics of Endometr ial Stromal Tumors I. Stromal nodule A. Pushing margins B. Loss than 10 mitoseq in 10 HPF C. Confined to the uterus D. No lymphatic or vascular invasion II. Endolymphatic stromal myosis A. Infiltration of myometrium B. Less than 10 mitoses in 10 HPF C. Vssctilar and lymphatic invasion common which may be massive giving rise to distinctive cross and microscopic patterns D. May extend beyond the uterus end con metastasize III, Stromal sarcoma A. Infiltrating margins, usually with extensive myometrial infiltration B. Greeter than 10 mitoses in 10 HPF C, Vascular and lymphatic invasion common D, Frequently extends beyond the uterus and metastases are common (45) APRIL 21, 1974 - CASE NO, U ACCESSION NO. 19913 MODERATOR'S DIAGNOSIS: Ma lignant Brenner tumor of the ovary, CLINICAL ABS TRACT: This 62 year old femal e presented with dul l pa~ and pressure in the left l~~er quadrant, She bad previously had a muc inous cystadenoma of the ovary removed. At laporatomy there was a cystic l eft ovarian tumor measuring 7 em . in diameter, The inside of the cyst wee lined with purpl e, fr'inble, papillary mater ial end in one portion of the wall there was a lobulated, multicystic, white and yellow mass, tiTCROSCOPIC DESct1PTION: The tumor is composed of proliferating masses of transitional like epithelium which are many cell layers thick, The cells are present over fibrous cores giving a papillary appearance to moat of the tumor. In other areas solid nests of tumors are present with a dense fibrous stroma. The tumor nests in the fitrous stroma are frequently cystic and many of the proliferating masses are lining cystic spaces. Mucin filled spaces are frequent within the epithel ium and many of the cells contain cytoplasmic mucin, par ticularly those near the surface of the cystic spaces. Mitoses are numerous tb~oughout the tumor and some mitoses are bizarre end abnorma l, Ther e is marked cellular atypia and anaplasia in focal areas. I n some areas of the stroma, islands of the cells are irregular and atypical, and appear to represent invasive malignant neoplasm, DI SCUSSION : The differential diagnosis in this case would include endometrioid carcinoma with squamous metaplasia. H~1ever , I think the cytologic features of the tumor cells suggest a resemblance to transitional cells of the bladder and this then would be a Brenner tumor . Whenever one diagnoses Brenner tumor, particularly one with this degree of atypia and number of mitoses, the possibility of me tastatic bladder carcinoma to the ovary baa to be excluded. Granulosa cell tumor is also a consideration when a Brenner tumor is considered. However, Call-Exner bodies are not identified in this tumor, pleomorphism is much more marked thon in the most granulosa cell tumors , and granulosa cell tumors do not contain PIIS positive ma terial. In addition, granulosa cells often contain cytoplasmic l i pid. Brenner tumors represent 1-2% of all ovarian tumors and occur at a mean age of 50 years (1,2). They have never been reported in children. Approxi· mately 80 to 90% of them are found as incidental findi ngs subsequent to an opphorectomy done for other reasons. Brenner tumors may become large (46) Page 2 APRIL 21, 1974 • CASE NO. 12 ACCESSION NO. 19913 and when they do, they can cause symptoms of abdominal pain and menstrual irregularities. Grossly, they are firm, gray uhite, sometimes yellm~ tumors which are usually unilateral but approximately 6 to 81. are bilateral. Microscopically they are composed of sheets and cords of epithelial cells embedded in a proliferative stroma, either ovarian stroma or fibrous tissue. n1e tumor cells nre uniform with few mitoses. Epithelium and stroma are usually d.istinct but may appear to merge . The nuclei of the tumor cells characteristically hove a lorigitudinal notch or ~;roove similar to the grooves found in sex cord cells. Cells containing cytoplasmic mucin are frequently found, and cyst formation, calcification and hyalinization are common. Cortical inclusion cysts are associated with Brenn.er tumors in many cnscs and about 107. of Brenner tumors are associated with mucinous cyst adenomas, 57. with serous cyst adenomas and 5% with cystic teratomas. The~e other neoplasms are usually on the same side as the Brenner tumor, but not exclusively. The histogenesis of the Brenner tumor is unkn~~n but most authorities agree that it arises from the surface (coelomic) epithelium of the ovary as suggested by Arey from serial studies (3) . The surface epithelium of the ovary is capable of differentiating into Hullerien structures t uch as mucinous and serous epithelium and urothelial epithelium such as that seen in the Brenner tumors and in Wolthard's cell rests (4). Other origins of the Brenner tumor such as from the follicle, the undifferentinted sex cord cells, and the rete ovarii have also been suggested bu ~ not sustantiated. Occasional Brenner tumors may be associated with hormone production, usually estrogen, and endometrial hyperplasia may be associated with these tumors. Alm6.st all Brenner tumors are benign; however, some Brenner tumors may have an unusual degree of epithelial proliferation, often papillary, resulting in a tumor which resembles a transitional cell carcinoma of the bladder (5). hs long as the tumor cells do not invade, and as long as there are not cytologic features of malignancy, these tumors have a benign course and have been desienated as proliferating Brenner tumors. Most proliferating Brenner tumors have no or minimal atypia, but mitoses may be found. ~~lignant Brenner tumors also occur and separation from the proliferatinc type may be difficult. hny Brenner tumor in which stromal invasion is present is malt!gn~~. hm~ever, determining ~1hether the nests in the stroma in Brenner tumor arc actually invasive or not is difficult. Miles and Norris have stated that if the proliferating epithelial nests contain cells which are cytologically malienant, the tumor should be considered a malignant Brenner tumor (6). On the other hand, Scully uill accept a Brenner tumor as malignant only if invasion can be demonstrated and thinks that lesions with carcinoma-in-situ should be considered t~ithin the realm of the proliferating Brenner tumor (7). (See Table 5) In the present case, there is certainly cytologic evidence (47) Page 3 APRIL 21, 1974 • CASE NO, 12 ACCESSION NO, 19913 of malignancy and in certain areas I have interpreted the nests as invasive rather than just Brenner nests wit hin the stroma. I would thus consider this case to represent a malignant Brenner tumor, Clinically the proliferating Brenner tumor usually occurs in an older patient than the benign type by about 10 years (5) , Most patients with proliferating Brenner tumors present with symptoms of pain, bacl REFERENCES : 1. Ehrlich, C.E. and Roth, L,M . : The Brenner tumor. Cancer 27 :332, 1971, 2. Silverberg, S.G.: Brenner tumor of the ovary. A clinico-pathologic study of 60 tumors in Sl1 women. Cancer 28:533, 1971. 3, Arey, L. B.: The origin and form of the Brenner tumor. Am. J. Obstet. & Gynecol. 112:91, 1972, 4 , Roth, L.M.: Fine structure of the Brenner tumor . Cancer 27:1482, 1971. 5, Roth, L,M, and Sternberg, l~ . H.: Proliferatinc Brenner tumors, Cancer Q:687' 1971. 6. Hiles, P.A. and Norris, H.J,: Proliferative and malignant Brenner tumor of the ovary. Cancer 1Q:l74, 1972. (48) Page 4 APRIL 21, 1974 - ChSE NO. 12 ACCESSION NO. 19913 7. Hallgrimsson, J. and Scully, R.E.: Borderline and malignant Brenner tumors of the ovary. Acta. Path. Suppl. 233:56, 1972 . 8. Hull, M.G .R. and Campbell, G.R.: The malisnant Brenner tumor. Obstet. & Gynacol. 42:527, 1973 . Table 5 Criteria for Proliferating & Malignant Brenner Tumors (Hallgrimsson and Scully) I. Proliferating (Borderline) Brenner Tumors Typo A: Single or several large cysts are lined by proliferotine epithelium often papillary ranzins in atypicality from none or slight to carcinoms-tn-situ. All abnormal epithelium is confined to the cysts and is not in the stroma and mitoses may be numerous. (B) Solid nests or small cysts in the stroma in which the epithelial cells are atypical but are not malignant. II. Malignant Brenner Tumors (A) S~oll cysts or solid nests are lined by or composed of cystoloeicolly malignant cells; large cysts may be present; invasion of the stroma by malignant transitional cell. Benign Brenner elements are associated with the ma l ignant epithelium. (D) Same as A except benign Brenner elements are not found. (50) APRIL 21, 1974 - CASE NO , 13 ACCESSION NO, 19739 MODERATOR'S DIAG~~SIS: Adenocarcinoma of the cervix, mucinous type, CLINICAL ABSTRACT: This 44 year old patient had an abnormal pap smear with cells present suspicious for malignancy. Examination revealed cervical erosions and a D&C and conization of the cervix were performed, The cone specimen showed multiple small cysts filled with mucinous material measuring up to .3 em. The cervical stroma was firm. The endometrial curettings revealed prolifera tive phase endometrium •~ith mild cystic chanzes, Following the conization the patient received radiotherapy. MICROSCOPIC DESCRIPTION: The overlying squamous epithelium in the cervix shows mild to moderate dysplasia. Beneath this epithelium are irregular gland spaces filled <>ith MUcin as well as large pools of mucin lined by cervical stroma and clusters of atypical cells. Many of these pools snd lal DISCUSSION: The main di APRIL 21, 1974 • CASE NO , ll• ACCESSION NO. 20207 MODERATOR'S DIAGNOSIS: Moderately differentiated adenocarcinoma of the endocervix with scirrhous areas CLINICAL ABSTRACT: The SB year old patient was noted to have bleeding from the cervix during examination end a biopsy was obtained, Foll~~ing the biopsy a total hysterectomy and bilateral ss1.pingo-oophorectomy l'ere performed. The cervi>; was hard up to the endometrial junction and apparently infiltrated by tumor . Foll~ing surgery the patient had cobalt radiotherapy end was seen a few months foll~ing the radiation therapy with no evidence of tumor . ~ICROSCOPIC DESCRIPTION: This adenocarcinoma sh~s several different histologic patterns. In most areas the tumor is a moderately to poorly differenti.ated adenocarcinoma infiltrating tho cervical stroma. In these areas the tumor is composed of_ poorly formed glands lined by moderately pleomorphic cells with mitoses. There is some cr~ding and in areas a cribiform pattern is noted. In other areas, the tumor is growing os solid sheets of cells with focal gland forma~ tion. The PAS 1~ith diastase stain s h~>s abundant mucin both intracellulsrly and within the glandular spaces. Other areas of the tumor, particularly at the bose, show neoplastic cells infiltrating the stroma in an Indian file patt ern without apparent glandular formation, In these latter areas there is considerable fibrous response to the tumor cells »ith little evidence of glandular differentiation. The tumor is deeply invasive and extends to the edge of the ~actions . DISCUSSION: One of the major problems in diagnosing adenocarcinoma of the cervix is to differentiate primary endocervical adenocarcinoma front primary endometrial adenocarcinoma. This can be very difficult but several features may be helpful, l, Differential curettage to determine the location of the tumor is essential. The presence of carcinoma and benign non neoplastic tissue mixed together does not indicate actual invasion, Before deciding carcinoma is present in either the endometrium or the endocervix, invasion of the stroma of these tissues should be demonstrated. It is common to contami nate the specimen with the tumor dur ing a diffarential curettage. t~hile differential curettage is extcmaly helpful in many cases, it does not aid in the situation in which adenocarcinoma is (52) Page 2 APRIL 21, 1974 - CASE NO. 14 ACCESSION NO. 20287 arising in one place and invading the other secondarily. In this circumstance, search for carcinoma- i n-situ can be extremely helpful, Abell has reported that approximately 4ot of primary adenocar cinomas of the endocervix will be associated >lith adenocarcinoma-in-situ in the surrounding glands. Li\(ewise atypical hyperplasia and in-situ in the changes in the endometrium can be helpful if the tumor is a primary endometrial carcinoma. 2. Histochemical staining may be useful (1) . Characteristically, adenocarcinoma of the endocervix produces both intracytoplasmic and intraglandular mucin >~b ile adenocarcinoma of the endome tr ium produces mucin within the glandular lumens and on the terminal bars of the cell. Intracytoplasmic mucin is unusual. However, it mus t be remembered that the entire spectrum of adenocarci nomas found in the cervix can also be found in the endometrium and vice versa. 3, The cell type of the carcinoma (2). It is very unusual to have a primary endome trial carcinoma of the we l l differen tiated endocervical type ~1h il e it b also unusual to have endoroetrioid carcinomas primary in the endocervix. Definition of the primary site of the adeno~carcinoma can be achieved in most instances by usins the results of the differ ential curettage, carefully searching the histolozic sections for carcinoma-in-situ; determin~n c the· cell type a£ the :arcinoma and doing mucin stains. Accurate determination of the primary site i s of importance since primary endometrial carcinomas will be treated by surgery and possibly radiation whereas pr imary endocervical carcinomas ore usually treated by r adiation alone. 1£ after the above procedures one is still uncertain as to the primary site , and there is definitely tumor in the endocervi x, the best course is to treet the patient as if she had a primary adenocarcinoma of the endocervix, since endometrial adeno carcinoma secondarily invading the endocervix wil l metastasize to t he regional lymph nodes in a pattern similar to that o£ primary endocervical carcinoma, In summary, this is a moderately differentiated cervical cell type of adenocarcinoma with areas of scirrhous differentiation, The tum~r demon,.. , strates the admixing of eell types frequently found in endocervical adenocarcinoma which makes classification somewhat difficul t. The prognosis in this case is guarded because of the poor differentiation of the tumor and the extensive infiltration noted in the histologic sections. Page 3 APRIL 21, 1974 - CASE NO , 14 ACCESSION NO, 20287 REFERENCES: l. Sorvari, T.B.: A histochemical study of epithelial muco- substances in endometrial and cervical adenocarcinomas. Acts Psthol, Microbial. Scsnd. 207 (Suppl) :1, 1969. 2. Abell, M. R. : Invasi ve Carcinomas of the Uterine Cervix. In Norris, H. J . , Hertig, A.T. and Abell, M;R. Eds: The Uterus lAP monograph Ul4, BaltUnore 1973. The Williams & Wilkins Co, p. 437 . (54) APRIL 21, 1974 - CASE NO. 15 ACCESSION NO. 20304 MOIJERI\TOR 'S DIAGNOSIS: Hetastatic malignant neoplasm, primary undetermined CA likely primary is breast) CLINICAL ABSTRACT: This patient presented with menometrorrhagia of one year's duration. Pelvic examination revealed a mass in the uterus consistent with a leiomyoma. X-ray' showed numerous radiotucent bony lesions suggestive of metastatic carcinoma. Some examiners felt a mass in the breast, others did not. Mammography was negative. Seruc cal cium, phosphorus and al kaline phosphatase were normal as was the serum electrophoresis. A SHIAA determi.nation was within normal limits. The uterus ~1aa removed and weighed 410 grams . There were numerous small leiomyoma& and one large intramural mass thought,. to be a smooth muscle tumor located in the fundus l~bich was tan and bad areas of hemorrhage and central cystic degeneration. MICROSCOPIC DESCRIPTION: Infiltrating the myometrium are groups and nests of ce1ls with uniform nuclei and indistinct cytoplasmic borders. Some of the tumor cells are arranged in large sheets while in other areas the tumor cells are in small clusters and groups. The tumor cell nuclei have delicate chromatin and some contain longitudinal grooves or notches. In some areas, the tumor cells are arranged in on acinar like arrangement but definitive Call-Exner bodies are not seen. Vessel invasion is prominent. Examination of the right ovary sh~1s similar neoplastic cells arranged in cords, as single files, and as individual cells mixed with stromal cells. The tumor cells are not forming Call-Exner bodies nor follicle like structures. In focal areas, the tumor cells are arranged in a pattern reminisc.ent of breast carcinoma. DISCUSSION: This malignant neoplasm metastatic to the uterus is difficult to classify. One of the major considerations is whether or not it represents metastatic granulosa ce 11 tumor. I seriously doubt this is granulosa cell tumor because I do not see definitive Call-Exnor bodies nor can I find the peripheral palisading of cells at the edges of the tumor nests which I associate with granulosa cell tumors. There is a tendency to diagnose poorly differentiated malignant neoplasms which vaguely resemble granulosa cell tumor as the neoplasm. Many different types of malignant neoplasms have patterns suggestive of granulosa cell tumors and to causCl further confusion at least 11 different types of histologic patterns have been described for granulosa cell tumor itself (1) . These include the so-called cylindroid, sarcomatous, pseudo adenomatoua, folliculoid and others. Tumors l·lhich resemble granulosa cell ~umors, but which do not have definitive histologic criteria, should be (55) Page 2 APRIL 21. 1974 • CASE NO. 15 ACCESSION NO. 20304 designated simply as tumor unclassified or sex cord tumors unclassified. Granulosa cell tumors have little variation in microscopic appearance and are composed of monotonous uniform round cells with slightly granular eosinophilic cytoplasm and indefinite cellular margins. The nuclei are small without atypia and frequently contain a longitudinal groove. Call·Exner ~odies are found in granulosa cell tumors and are an important diagnostic feature. Call·Exner bodies should not be confused with the acinar structures of adenocarcinoma. They are formed by granulosa cells with the nuclei toward the center of the Call·Exner body and the bulk of the cytoplasm more peripheral (2). In the center is pink material or a degenerating cell but not a blood vessel. This central material is basement membrane matrix. Call·Exner bodies. as opposed to acini of adenocarcinoma, have an indefinite central cytoplasmic margin which is fuzzy rather than sharp. Acini are not formed. Gr c nulos~ ce lls are negative for glycogen and mucin and mitoses are very xare and difficult to find . Tumors which do not conform to these histologic criteria should not. in my opinion. be diagnosed as granulosa celi tumors. Granulosa cell tumors ore rarely malignant or aggressive. A study at the Armed Forces Institue by Norris ana Taylor, using life table survival statistics, showed patient survival for granulosa cell tumor to be 971. at five years and 931. at ten years (2) . Very few patients die from granulosa cell tumors and aggressive tumors almost always involve pelvic recurrences or metastases to the pelvis rather than widespread distant metastases. I have never heard of a granulosa cell tumor with extensive bone metastases as are apparently present in this case. In summary. strict criteria should be used to diagnose granulosa cell tumors and tumors which do not meet the histologic criteria should not be classified as granulosa cell tumors or granulosa cell carcinomas. tHdely metastasizing tumors are unlikely to be granulosa cell tumors. On the basis of the above criteria. I do not think that the tumor in this patient's uterus is a granulosa cell tumor, The second consideration in the differential diagnosis is metast atic breast carcinoma. The tumor nests are similar to those found in metas tatic breast carcinoma and nuclear grooves can be found in breast carcinoma cells. In addition, a 1~~ mitotic rate is rather characteristic of some types of 4octol and lobular carcinoma. The negative mammogram is of course. interestint but I think it probably should be repeated and other techniques such as thermography or xerography considered. On the basis of the histologic findings. the extensive bony metastases. end the difficulty of detecting primary breast carcinoma. I think the primary is most likely in the breast. (56) Page 3 APRIL 21, 1974 • CASE NO. 15 ACCESSION NO . 20304 The third possibility is a carcinoid. The cords and ribbon like arrangement of the tumor as well as the nuclear uniformity suggest carcinoid, H~1ever , the argentaffin s tain is negative, as is the SHIM determination, and the patient does not have the carci noid syndrane. The histologic pattern of the tumor in the ovary does not part icularl y resemble carcinoid although carcinoid is very difficult to absolutely exclude, Ovarian carcinoids arise most often from respiratory and gastrointestinal epithelium in cystic teratomas but can arise in other types of ter atomao , in mucinous tumors, and can occur as primary tumors in the ovary. They may .. also be metastatic from other sites. Small intestinal carcinoid& are particularly notorious for givins r i se to larce ovarian metastases. All the primary ovarian carcinoids thus far reported have been unil ateral and only one has metastasized. Approximately a third of primary ow:rian carcinoid are associated ~~ith the carcinoid syndrome in the absence of metastases (3) , Other considerations in t he differential diagnosis woul d be mye loma but the tumor cells do not resemble plasma cells and the MGP s t ain was negative. Another consideration is metast atic paraganglioma because of t he boll arrangement of some of the tumor cell mass (4) . Ro.•ever, these are not \·tell formed zell-bsllen and the histol ogic pattern docs not particularly resemble paraganglioma to me . REFBRBNCES : l, Novak, E, R,: Feminizing gonadal stromal tumors. Obste t. & Gynecol. ~ : 701, 1971 . 2 . Norris, H. J . and Taylor, H. B.: Prognosis of sranulosa-theca tumors of the ovary. Cancer ~: 255 , 1963. 3, Scully, R. E.: Recent progress in ovarian cancer, Rum. Pathol. !:73, 1970. 4. Abe ll, M,R, , et al . : Tumors of the peripheral nervous :system. Hum, Pathol. ,1:503, 1970. POLL OI~ •ll1': (Dr, Charle s Haskell) Most recent information ~~hich was unavailable to Di" . R-ichard Kempson at the time of the seminar is as foll017S: ''Exami.nation of bone mar r011 at UCLII in September 1973 reveal ed tumor cells and radiograph exhibited multiple destructive bone l esions. The patient was treated 1-lith alkeran and is reported to be relatively stabl e with good clinical response to treatment as of Septem ber 1974. The primary site of t he neoplasm has not yet been clearly deli neated. " (57) APRIL 21 , 1974 - CASE NO . 16 ACCESSION NO. 11830 MODERATOR 'S DIAGNOSIS: Papillary adenofibroma of the endometrium. CLINICAL ABSTRACT: This 71 year old female presented with a history of intermittent vaginal bleeding of 8 months' duration. A hysterectomy was done. Within the ondoJ ' . metrial cavity there was a 4. 0 x 2.5 em. mass of cystic, papillary and nodular tissue attached to the posterior and lateral l1alla of the uterus. MICROSCOPIC DESCRIPTION: Present in the endometrial cavity is a mass containing stroma and epithelium thrown up into pol ypoid branching masses with prominent cleft formation. The cystic spaces and cleftsform blunt papil lary folds which protrude into the cystic spaces. Endocervical, endometrial and squamous epithelium are all focally present lining the papillae. Some of the papillae ar e denuded of epithelium. The atr0ma is hyalinized and focally myxoid with spindle cella in a whorled pattern. Mitoses are very rare and there is no evidence of atypia or malignancy. DISCUSSION: Papillary adenofibroma appears to be the benign counterpart of the malignant mixed Mullerian tumor. It might conceivably be called a benign mixed ~!ullerian tumor but such terminology could lead to confusion with malignant mi xed Mullerian tumor . Since the les.ion has many similarities to the adeno fibroma of the ovary, it is beat designated as a papillary adenofibroma, as suggested by Abell who described 3 cases arising in the cervix (1). Papillary adenofibroma is a l esion in which there is both mesenchymal and epithelial proliferation and both elements are histologically benign, Clinically, patients l~ith this lesion present Hith vaginal bleeding and are usually in an older age group. The mass may protrude from the cervix. All adenofibromas thus far reported have been benign with the exception of one of the cases reported by Vellioa, et al. which contained focal adenocarcinoma in one portion of the lesi on (2). The differential diagnosis must include endometrial polyps but the polypoid· masses within cystic spaces, the cleftine, the hyalinized stroma and the club shaped papill ae should serve to separate this lesion from the usual endometrial polyp. In addition, papillary adenofibromas contain endocervical as well as squamous and endometrial epithelium, Malignant mixed Mullerian tumors have a similar proliferation of epithelial and mesenchymal elements. However, both t he epithel ium and the mesenchyme are malignant in malignant Mullerian tumors while both elements are benign in the papillary adenofibroma. Submucous adenomyoma contains both smooth muscle and endometrial glands and has some (58) Page 2 ArRIL 21, 1974 - CASE NO, 16 ACCESSION NO. 11830 resemblanc:e to tho papillary adenofibroma. However, it docs not sho.t the intracystic papillary clubbing and the clefting which are characteristic features of papillary adenofibroma. The stroma of papillary adenofibroma can be cellular and myxoid and cere must be taken not to confuse it with embryonal rhabdomyosarcoma or the other sarcomas. REFERENCES: 1. Abell, H. R. : Papillary adenofibroma of the uterine cervix. Am, J. Obstet, and Gynec, 110:990, 1971. 2. Vellios, F., et al.: Papillary adenofibroma of the uterus. Am. J. Clio. Path. 60:543, 1973. (59} APRIL 21, 1974 • CASE NO. 17 ACCESSION NO. 20565 MODERATOR'S DIAGNOSIS; Sex cord mesenchymal tumor with annular tubules CLINICAL ABSTRACT: This 25 year old female had a 4 year history of irregul ar menses with periods of amenorrhea. A dilatation and curettage revealed mild hyperplasia of the endometrium. Three years prior to admission a left adnexal mass ~1as noted which slowly increased ·in size. At the time of operat ion there «as a 6 em. mass replacing the left ovary and involving the posterior lecf of the broad ligament. The r i ght ovary ~las unremarkable. The tumor l~as solid, bosselat ed, tan-yellow, and measured 6 em. in diameter. MICROSCOPIC DISCUSSION: The tumor ia composed of rounded epithelial nests of varying size containing eosinophilic hyali.ne bodies with barely perceptible lamination. These hyaline bodies coalese to form complex neruorlts 1dthin some of the nests and are continuous ~lith the basement membrane material outside the nests. This matrix also separates many of the nests of cells. Most of the nuclei of the tumor cells are arranged at the base of the cella and have small inconspi cuous nucleoli. TWo patterns can be discerned in the epithelial masses: Firstly, closed tubules wit h hyaline bodies at the center, and secondly, a network of continuous tubules arranged about numerous hyaline bodies. Longitudinal solid tubules are also noted. Bet'l~een some of the nest there is ovarian strom~ and foci of calcification are scattered about the turuor. The hyaline material is PAS positive and congo red negative. DISCUSSION : Sex cord mesenchymal tumor with annular tubules i s a distinctive and rare overian tumor which should be separated from granulosa cell tumor and Sertoli cell tumor (1). The tumor bas been reported to occur in patients from 11 • 64 years of age, and some , but not all, of the pa tients with this tumor also have the Peutz-Jegher syndrome !·lith oral melanosis and gastrointestinal hamartomatous polyps. Se:: cord mesenchymal tumor with annular tubules is also the most common ovarian tumor encountered in patients with the Peutz Jegher syndrome . Four patient s in Scully's series (1} had endometrial cystic hyperplasia associated with sex cord tumor and one patient IMS sterile. Grossl y, sex cord mesenchymal tumors with annular tubules are soft to firm, yellow, and solid. Bilateral involvement occurs in about 20% of the cases . A germinoma has been found in t he oppos ite ovary in one patient with an XY genotype. the tumors range from microscopic up to 17 em. and may be multiple. (60) Page 2 APRIL 21, 1974 - CASE NO. 17 ACCESSION NO, 20565 The neoplasm that sex cord mesenchymal tumor most resembles is granulosa cell tumor, which may rarely have tubules and can contain hyaline bodies and plaques of basement material, although these structures are unusual (1,2). However, granulosa cell tumors do not undergo calcification and the nuclei in the sex cord tumor do not have the prominent nuclear grooves which are seen in granulosa cell tumors. Sertoli cell tumors are not calcified but do contain tubules which look similar to those in the annular t umor . However, hyaline plaques are most unusual in pure Sertoli cell tumors. Topographically sex cord mesenchymal tumor appears to be a granulosa cell tumor which is growing in a tubular fashion similar to the Sertoli cell tumor . Sex cord mesenchymal tumor is not a gynandroblastoma which bas mature granulosa cells ~1ith Call-Exner bodies and typical Sertoli tubules with Leydig cells containing l«'inko crystaloids. Leydig cells are not found in the sex cord mesenchymal tumor, Some areas of the sex cord tumor resemble a Brenner tumor, h~~ever, the mucin producing cells charactcristic·of. Brenner tumor are not present. In addition, the tumor cells do not look like transitional 'cella, tu ular structures with peripheral nuclei are not seen in the Brenner tumor, and nuclear grooves not found in the sex cord tumor, are characteristic of the Brenner tumor. Sex cord mesenchymal tumor with annular tubules resembles gonadoblastoma since both tumors contain calcium and have PAS positive hyaline material be~~een the cells and around the tumor cell nests and tubules (3), H~oever, germ cells are always_pre.sent within.. the nests i .n gonadoJ?lastoma and are no:!C..found in sex cord tum~!!_, this fea-ture al-lows ea~zy=separation of the ~•o tumors . Gonadoblastoma frequently contains Leydig-liko cells in the stroma. We have recently completed an ultrastructural study of conedoblastoma and are finishing a similar study of&£¥ cord tumo~ (4), The hyaline material in both tumors is similar and appears to be formed by the Sertoli/granulosa type cells in the nests and tubules, Thus far, all sex cord mesenchymal tumors have been benign, Although many of the patients who have sex cord mesenchymal tumor also have the Peutz-Jegher syndrome, it is not found exclusively in such patients, The present patient apparently does not-have the Peutz-Jegher syndrome. Approximately 57. of females \·lith the Peutz-Jegher syndrome have ovarian tumors, which ere of a wide variety of types,.but the most common type is sex cord tumor ~~ i th annular tubu lea • Reproduced in Table 6 is our working classification of the sex cord stromal tumors of the ovary. This is based on the recent WHO classification as well as the FICO classification (5). It is hoped this international classification will be universally used, Sex cord tumor is placed with the unclassified tumors since its histogenesis is obscure. The sclerosing stromal· (61) Page 3 APRIL 21, 1974 - CASE NO, 17 ACCESSION NO. 20565 tumor is o benign sex cord tumor recently described by Chalvardjian and Scully (6) . It is similar to the fibromas and thecomas but differs from them by having marked vascularity, cellular pleomorphism, sod a prominent tendency to undergo sclerosis. The category of lipid cell tumor is reserved for those tumors composed of cells with clear to eosinophilic cytoplasm in ~1hich crystalloids of Reinke cannot be found and l·lhich are not luteomas. Interestingly, Sternberg and Roth have recently described sex cord tumors arising from the stroma which contain neoplastic Leydig cells with cytoplasmic crystalloids of Reinke (7,8). We agree that these latter tumors should be classified separately as stromal Leydig cell tumors or pure Leydig cell tumors, non hiler type , and the term lipid cell tumor should be used only f or neoplasms whose histogenesis is uncertain. REFERENCES : 1. Scully, R. E.: Sex cord tumor with annular tubules. A distinctive ovarian tumor of t he Peutz-Jeghers syndrome . Cancer 25:1107, 1970. 2. Norris, B, J. and Taylor, B. B. : Prognosis of granulosa-theca tumors of the ovary. Cancer ~:255, 1968, 3. Scully, R. E.: Gonadoblastoma . A revi el~ of 74 cases. Cancer 25: 1340, 1970. 4. Hou-Jensen, K. and Kempson, R. L. : The ultrastructure of gonadoblastoma and dysgerminoma. Bum. Path, 5:79, 1974 . 5. Serov, s. F. and Scully, R. E. : Histologic typing of ovarian tumors. Geneva 1973 l•lorld Health Orgcnization. 6. Cha1vardjian, A. and Scully R. E.: Sclerosinc stromal tumors of the ovary. Cancer 31 :66l,, 1973. 7. Sternberg, H. H. and Roth, L. M.: Stromal-Leydiz cell tumor and non neoplastic transformation of ovarian stroma to Leydig cells. Cancer 32: 940, 1973 . 8. Roth, L. M. and Sternberg, 1~ . H. : Pure Leydig cell tumor, non hiler type. Cancer 32:952, 1973 . (62) Page 4 APRIL 21, 1974 - CASE NO, 17 !CCBSSION NO, 20565 TABLE6 CLASSIFICATION OF SEX CORD TUMORS OF THE OVARY (l~ORLD HELIL'IH ORGANIZATION) (5) Sex Cord Stromal TUmors A, Granulosa-stromal cell· tumors 1. Granulosa cell tumor 2. 'l\hecoma. l:ibroma croup 3. StTowal luteoma 4. Sclerosing stromal tumor B. Sertoli-Leydig cell tumors (Androblastoma) l , ~lell differentiated a) Tubular adenoma (pure Sertoli cell tumor) b) Tubular adenoma with lipid storage (Sertoli cell tumor with lipid storage) c) Tubular adenoma with Leydig cells (Sertoli-Leydig cell tumor) d) Leydig cell tumor; Hiler cell tumor 2. Intermediate differentiation 3, Poorly differentiated C. Lipid (lipoid) cell tumor (of indeterminate cell type) D, Gynandroblaatoma E, Unclassified l, Tumor with annular tubules 2. Too poorly differentiated to identify cell types (63) APRIL 21, 1974 - CASE NO. 18 ACCESSION NO. 20562 MODERATOR'S DIAGNOSIS: Mullerian adenosarcoma of the uterus (heterologous element of rhabdomyosarcoma) CLINICAL ABSTRACT: This 43 year old female bsd regular menses until 6 '~eeks prior to admission when she developed continuous vaginal bleeding. Examination revealed · a fungating, friable, soft mass which filled the upper vagina. The hysterec tomy specimen showed the cervix to be replaced by a 6.0 x 6 .0 x 5. 0 em . fungating , necrotic, papillary tumor . On opening the endocervical canal, the tumor tissue extended up into the uterine cavity. MICROSCOPIC DESCRIPTION: This tumor i s infiltrati ng and replacing portions of the endometrium. The tumor cells ere spindled to cuboidal and contain numerous mitoses which in some areas exceed 10 per 10 high power fields. Some of the neoplastic cells have elongate eosinophilic eytoplasm and definite eross striations can be identified in most of these tumor eells. Other tumor cells have rather clear cytoplasm '~ith indistinct margins. Focally, there is edema with a more myxoid appearance to the stromal cells. These cells appear to be mesenchymal and are histologically malignant. Embedded '~ithin the mesenchymal portion of the tumor are glandular struetures which are lined by histologically benign cells. Surrounding these glands is a eollar of edematous spindled stroma. Histologically, the mesenchymal element of the tumor appears to be a combination of rhabdomyosarcoma, leiomyosarcoma and undifferentiated sarcoma. The sareomatous portion of the tumor also infil trates the myometrium superficially in one area. DISCUSSION: The differential diagnosis of this neoplasm 1~ould include pure rhabdomyo sareoma of the uterus. Rhabdomyosarcomas do occur in the uterus, most often in association vrith malignant mixed Mullerian tumors, but they may be pure as in embryonal rhabdomyosarcoma of the cervix seen most frequently in childhood and in the pleomorphic rhabdomyosarcoma occasionally encountered in adults (1,2) . However, it is not entirely clear that all of the "'esenchymal elements in this tumor ore rhabdomyosarcoma end this could be a mixed leiomyosarcoma and rhabdomyosarcoma . In any case, the presence of ~lands in the tumor makes the diagnos is of pure sarcoma diffi cult. One could conolude that the glands are normal endometrium which has been surrounded by the mesenchymal proliferation but it would be most unusual for a malignant mesenchymal tumor to surround rather then obliterate normal endometrial glands. Malignant mixed }1ullerian tumor also has to be considered but the epithelial (64) Page 2 APRIL 21, 1974 - CASE NO, 10 ACCESSION NO. 20562 clements in malignant mixed Mullerian tumor are always malignant. This neoplasm, then, does not fit well into any of the previously described t ypes of uterine sarcomas. I have observed neoplasms of this type and have been puzzled as to '~hat terminol ogy to use for them, Recently, Clement and Scully have collected seven or eight tumors of this type and have coined the term Hullerian adenosarcoma of the uterus to described them (3) . The term encompasses the Mullerian ori3in of the neoplasm, the sarcomatous nature of the mesenchymal portion and the benign nature of the epithelial elements. Characteristically, Mullerian adenosarcoma of the uterus occurs as large masses in the uterus of older women. The most common presenti ng symptom is abnormal vaginal bleeding. The benign glandular elements are surrounded by a collar of compressed cells whil e the malignant stromal elements may be any of a number of different sarcomas including both heterologous and/or homol ogous types, Rhabdomyosarcoma has been observed in these neoplasms by Clement and Scully. It is impor.tant to separate Mullerian adenosarcoma from the pure sarcomas and from malignant mixed Mullerian tumors since Mullerian adenosarcoma has a better prognosis, Most of the patients with t his neoplasm do well and apparectly the only patients to develop metastases are those who have deeply invasive and extensive neo plasms at the time of hysterectomy. Tumors which are only superficially invasi ve rarely ever metastasi ze. This is in contrast to malignant mixed Mullerian tumor which may develop metastases even though the tumor is only superficially invasi ve. If the sections are representative of the extent of invasion, I would expect a good prognosis for this patient. However, the gross photographs suggest rather ext ensive invasion. Three different types of uterine mixed Mullerian tumors have now been described. Firstly, the tumor in which both sarcoma and carcinoma are present, i.e. glandul ar and mesenchymal elements are both malignant, is designated as malignant mixed Mullerian tum01: A second type, composed of sarcoma 1~ith benign glenda, is desienated as Mullerian adenosarcoma. A third type, in which both the stroma and the glands are benign, is designated as papillary adenofibroma. Theoretically, there should be a neoplssm wi·th carcinoma and benign stromal elements. Although this probabl y occurs, it i s obvious that separation from ordinary carcinoma is aLmost impossible and such a t umor uould be difficult to recognize. (65) Page 3 APRIL 21, 1974 - Cl\SE NO. 18 ACCESSION NO. 20562 REFERENCES : 1. Donl~ ra, B. et al.: Rhabdomyosarcoma of the corpus uteri, Am. J . Obstet, & Gynecol. 114:1025, 1972. 2. Hilgers, R,D.: Embryonal rhabdomyosarconla (botryoid type) of the vagina, Am. J, Obatet. & Gynecol: 107:484, 1970, 3, Cle~ent, R. end Scully, R,E.: Mullerian adenofibroma. To be published Cancer 197 4. (66) APRIL 21, 1974 - CASE NO. 19 ACCESSION NO . 12141 MODERATOR ' S DIAGNOSIS: Pl exiform tumor {tumorlet) of the ut erus. CLINICAL ABSTRACT: Tbts 44 year old pati ent had complained of irre~ lar menstrual periods and prolonged heavy fl~~ for many years. She stated that she never had a regular menstrual cycle. A hysterectomy and bilateral salpingo-oophorectomy '~as done. Serosal nodules, measuring up to 0.6 em. ~1ere present on the uterus and there was a bulsing pink-tan 2 em. mass present i n the fundus. The entire myometrium ~1as speckled ,.,~.th innumerable slightly raised, llray ,.,hite areas, measuring 0. 2-0.6 em. in diameter. Both ovaries contained endometriosis. MICROSCOPIC DESCRIPTION: Hithin the endometrium and the myometrium are nodular m(lsaes of cello '~hich tend to be sharply demarcated from the surrounding tissues. In the endometrium, the masses appear to be infiltrati113 the endometrium whil e they are more circur.~scTibed in the myometTiUiil. !lithin the gToups, the indivdual cells have indistinet cytoplasm and crumpled' but bland nuclei. In most STOups, the nuclei are aTTaneed in elongated cords and tend to be crowded to~etheT and separated by hyaline material. Nucleoli are inconspicuous and mi toses are not found. Blood vessels and capillaries are not prominent. Overall, the histologic patteTn is distinct ive and not indicative of malignancy . By tTichrome stain, the tumor cell cytoplasm is Ted and reticulin staining shows gTOups of cella surTounded by reticulin. DISCUSSION: Pl exifonn tumoTs of the uterus aTe benign lesions, usually found inci dentally in hysterectomy specimens. There have been appToximately thirty five cases reported {1,2,3,4,5). Characteristically, plexiform tumoTs are present at the endometrial-myometrial junction end occasionally aTe found i n both the endometrium Otld the myometrium. It is most unusual for them to be as laTge and diffuse as in this case, and I know of only ono other instance with this degTee of involvement and apparent multicentric pattern. There are no known symptoms from the lesion and it seems to occur most commonly i n ~1omen older than age forty. All except one of the TepoTted patients have had leiomyoma& as well as the plexifoTm tumor (6) . The histogenesis of plexiform tumors is uncertain; it has been suggested that they aTe voeculaT tumors , either glomus type OT capillaTy hemangiomas. In one of the cases repoTted from Memorial Hospital, a plexifoTm tumoTlet developed in a focus of adeno myosis suggesting endometrial stromal oTigin (5) . The tumor cells closely resemble normal endometrial stromal cells and their fTeqenc occurrence at (67) Page 2 APRIL 21 , 1974 - ChSE NO, 19 ACCESSI ON NO, 12141 the junction between the endome t rium and myometrium also supports a stromal origin, However, there is no proof that these are indeed stromal cells. The paucity of vascular spaces and the lack of resemblance to other vascular tumors as we ll as the pattern of reticulin fibers makes it extremely unlikely that these are hemangiomas, g.lomus tumors or hamangiopericy,tomas, h recent ultrastructural study suggests smooth muscle origin because of fibrils in the cytoplasm of the tumor cells (6) , However, basement membranes, a feature of normal smooth muscle., were not found , Fixation for the ultrastructural studies was not ideal, and confirmation of the findings should be obtained, There is some resemblance be~1een plexiform tumors and the so-called "bizarre" smooth muscl e tumors . We think plexiform tumor is a better name tbon plexiform tumorlet because the lesions can be large as in this case. The differential diagnosis of plexiform tumor would incl ude the bizarre leiomyomas si nce this form of smooth muscle tumors may have a variety of different histologic pa tterns and, indeed, plexiform tumor may be derived from smooth muscle. Another lesion to be considered in the differential diag nos~o io odenomatoid tumor which con involve the uterus. When it does , it most commonly occurs near the serosa, but can be located deeper in the myometrium, Plexiform tumor has an entirely different histologic pattern than the glandular structures embedded in connective tissue and .smooth muscle characteristic of adenomatoid tumor. The importance of rec·OGnizing plexiform tumors is not to confuse them with malignant neoplasms particularly metastatic carcinoma, and to recognize them os benicn haroless lesions. REFERENCES: 1 . Bader, L. V: Multicentric plexiform tumor lets of the uterus, PatholOgy _:!: 167, 1971. 2. Cera, P.J. : Plexiform tumorlet of the uterus. Am , J , Clin. Path, 59 : 263, 1973. 3. Budinger, J,H, and Greene, R.R. : A distinctive tumor of undetermined origin, Cancer 17:1155, 1964, l,, Potchefsky, A.S . : Plexiform tum~rlet of the uterus, Report of a case. Obatet, & Gynecol, ~ : 592, 1970,' 5. Larlig, G,G, et al,: Plexiform tumorlcts of endometrial stromal origin, Amer , J, Clin. Pathol, 44:32, 1965, 6, Goodhue , ~1 . 1~ . et al;: Smooth muscle origin of uterine plexiforn tumora . Arch. Pathol. 97:263, 1974. (68) APRIL 21, 1974 - CASE NO, 20 ACCESSION NO. 20056 MODERATOR'S DIAGNOSIS: Extramedullary myeloblastoma (granulocytic sarcoma, chloroma). CLINICAL ABSTRhCT: This 27 year old Caucasian female presented Hith a pelvic mass of five months' duration. Some years prior to admission she had had bilateral mastectomies for malignant tumors . A blood count on admission shot·led o Hhite count of 10,400 with 25~ blast forms. At laparotoJIIY. there "as a large firm pelvic mass arising from the uterus and involving loops of small bowel, the colon, and the side walls of the pelvis, The liver and spleen appeared normal, althouzh both were slightly enlarged. There flere numerous tumor implants over the omentum, Grossly, the tumor was green and involvecj, and markedly distorted, the uterus and both adnexa so that the ovaries could not be recognized, It fiBS irregular, focally friable, necrotic, and contained eelatinous thick material. MICROSCOPIC DESCRIPTION: The myometrium and endometrium are infiltrated by cord& and files of cells flhich do not form cohesive masses. The nuclei are vesicular, irregular, and frequently indented 1'1ith overlapping nuclear segments, Nuclear moulding is prominent and nucleoli are inconspicuous. Mitoses are easily found. In some cells the cytoplasm is indistinct, while in others it is more abundant and eosinophilic, Eosinophilic myelocyte& are mixed amongst the tumor cells . The napthol-ASD-chloroacetate esterase stain is positive in many of the tumor cells and cha~acterized by bri ght red cytoplasmic staining. The MGP stain is negative. DISCUSSION: One of the most important considerations in the differential diagnosis of extramedullary myeloblastoma involving the uterus is stromal sarcoma. In stromal sarcoma , however, the nuclei are more regular, the chromatin pattern is not as coarse, the ASD-chloroacetatc stain (esterase stairi) is negative, eosinophils are rarely found, and the tumor cells are cohesive with scant cytoplasm. Histiocytic lymphoma is also a consideration. H~~ever, the tumor cells in this case have too little cytoplasm for the usual histiocytic lymphoma, t:he nucleoli are not prominent as would be expected, and the napthol ASD-chloroacetate stain is negative in histiocytic lymphoma. Plasma cell mye loma is unlikely since the morphology of the tumor cells does not resemble , that of plasma cells, the esterase is positive, and the MGP stain is negative, which is exactly the reverse of the histochemical reactions characteristics (69) Page 2 APRIL 21, 1974 - CASE NO. 20 ACCESSION NO. 20056 expected in plasma cell myeloma . Undifferentiated carcinoma must also be considered but can be ruled out with the histochemical stains. In addition, eosinophile are present in this tumor in large numbers, a feature ~1hich would be most unusual for all the tumotsdiscussed above . Therefore, the combination of the morphology, the positive ASD-chloroacctate esterase stain, and the negative MGP stain indicate this is extramedullary myeloblastoma. Extramedullary tumors of myelogenous origin are often designated as granulocytic sarcoma although extramedullary myeloblastoma is a preferable term (1,2,3) . When the tumor masses are green, they are often designated as chloromas, The green color preaent in some extramedullary myeloblastomas is due to the presence of the enzyme myeloperoxidase ~hich occurs in myelo genous cells (1) . The fact t hat some extramedullary myeloblastomas are green and others are not, is probably due to the amount of this beme enzyme present and/or its oxidation state, The green color fade& on exposure to air and may be re-induced by hydrogen peroxide, Myeloblastomas are not all that rare. A recent aeries from Harvard contained fifteen cases in a series of 476 cases of leukemia (1). They may occur in chronic myelocytic leukemia as well as in acute myelocytic leukemia and the presence or absence of the green col or has nothing to do with the cell type. t1yeloblaatomas may be found within any organ end are usually discover Diagnostic problems arise for the pathologist ~1 hen extramedullary myelo blastomas develop in extradeullary tissues concurrent with or preceding the leul Page 3 APRIL 21, 1974 • ChSE NO, 20 ACCESSION NO, 20056 Some tips to help avoid errors in diagnosis in conjuction •~ith myelo blastomas are as follows: 1. Thinlt of the possibility of extramedullary myeloblastoma in all undifferentiated malignancies; particul arly look for eosinophile in al l undifferentiated neoplasms and in neoplasms i n whi ch the diagnosis of histiocyti c l ymphoma iR considered. 2. Always do imprints when lymph node biopsies are performed. Imprints stained with Romanofslcy's stain ~lill help identify mye l ocytic differentiation. 3, Utilize the ASD- chloroacetate atain•for esterase whenever the possibility of myeloblastoma is considered. The stain can be done on paraffin sections and visualizes esterase specific for neutrophile, neutrophil precursors, and mast cells. We use the Leder modification of the procedure originally described by Maloney et sl.(lO) . Cells contain ing the este····; ~ shm~ bright red cytoplasmic staining with this technique. The enzyme is resistant to histologic procedures and will persist after prol onged storage in paraffin. 4 . Electron microscopy can be hel pful in identifyi ng charac teristic myel •.cytic granules in tumor cella. ·. In summary, ext~~med~llexy myeloblastoma can be accurately diagnosed by careful histologic examination, histochemical techniques.and imprints. Althoush rare, it must be considered whenever undifferentia·ted neoplasms are encountered. REFERENCES: 1. Muss, H. B, and Moloney, W, C. : Chloroma and other myeloblastic tumors. Blood ~:721 , 1973. 2. Hiornik, P.R. and Seyrick, A.A.: Granulocytic sarcoma (chloroma) . Blood 35:361, 1970. 3. Liu, P.R. et sl. : Autopsy study of granulocytic sarcoma (chloroma) in patients with myelogenous leukemia, Hiroshima-Nagasaki 1949-1969, Cancer 31:948' 197 3. 4. Haaon, T.E. et a1.: Granulocytic sarcoma (cblorCilla) tl~o years preceding myelogenous leukemia. Cancer 1!:423, 1973, (71) Page II APRIL 21, 1974 - CASE NO. 20 ACCESSION NO . 20056 5, Lusher, J .N.: Chloroma as a presenting feature of acute leui 7. Garfinckle, R. S. and Bennett, D.E.: B~tramedullary myeloblastic trans formation ~n chronic myelocytic leukemia simulating a co-existent malignant lymphoma. Amer. J, Clin. Pathol. 51:638, 1969. 8. Gralnick, H.R. and Dettman, K. : Development of myeloblostama with massive breast and ovarian involvement during remission in acute leukemia. Cancer 24:746, 1969. 9. Lancet editorial: Chloroma confusion. May 19, 1973, p, 1099. 10, Leder, L. D. : The selective enzymocyto-chemical demonstration of neutrophil myeloid cells and tissue mast cells in paraffin sections. Klinische Wochenschrift 42:553, 1964. (72) APRIL 21, 1974 - CASE NO. 21 tCCESSION NO. 20542 MODERATOR'S DIAGNOSIS: Endometrial hyperplasia Nith intra~;landular morules (metaplastic change) . CLINICAL ABSTRACT: This 32 year old female presented with uterine bleeding ot three months' duration. A D&C and then a total hysterectomy were perfonned. The endo cervical lining and the endometrial mucosa appeared diffusely hemorrhagic and focally roughened. MICROSCOPIC DESCRIPTION: Some of the tissue fragments in the curetting& are normal proliferative endometrium, while other fragments contain increased numbers of glands with focal budding and crowdi.ng. In these latter areas, there are sheets of bland cella with regular nuclei and abundant cytoplasm repl acing portions of the glands and extending out from the glands into the stroma. Necrosis is present in some of these sheets of cells but mitoses are very rare. No malignant criteria can be found. Some of the cells are spindled, but no intercellular bridges and no keratin can be identified. The overall appearance of these sheets of cell suggest they originate from the glands and gr~i outward into the stroma, resulting in fusion of the masses. In the hysterectomy specimen, the endometrium shows less active hyperplasia, but the morules are still present. DISCUSSION: Intr aglandular morules are an important lesion because they may be misdiagnosed as carcinoma. The sheetlike arrangement of these metaplastic cells can cause obliteration of the endometrial architectu·re similar to that seen in well differentiated adenocarcinoma with squamous metaplasia. However, the cells are cytologically bland and do not demonstrate malignant criteria. The glenda associated with the morules are also benign. The cells in the morules do not contain mitoses, there is no pleomorphism, and the cells are uniform with abundant cytoploall'. Although l~ell differentiated adenocarcinoma may have bland metaplastic areas auch as is seen in squamous metaplasia, the glandular structures in adenocarcinoma ore malignant, unlike those seen in association with morules. Another malignant neoplasm which may be confused ~>itb morule formation is mixed adenocarcinoma and squamous cell carcinoma. In that entity, both elements are neoplastic end there are malignant criteria in both the adeno matous end squamous cells. Such features are not found in this case. Pure squamous cell carcinoma may also occur in the endometrium but intercellular (73) Page 2 APRIL 21, 1974 - CASE NO. 21 ACCESSION NO. 2051,2 bridges and/or keratin must be demonstrated before diagnosing a malignant neoplasm as squamous cel l carcinoma (1). Other types of metaplasia can occur in the endometrium and resemble morules (2). One of these is the so-called papillary surface metaplasia in which the cell cytoplasm is eosinophilic and abundant, and the nuclei are large, regular, and vesicular without atypia. Such eosinoph·ilic surface metaplasia may be papillary ·and can be confused with so -~alled carcinoma in-situ of the endometrium. However, there is no nuclear a typia as would be present in carcinoma-in-situ. Surface eosinophilic metaplasia probably represents a r egenerative phenomenon ond is often seen in patients receiving estrogens. Tubal metaplasia may also be found i n the endometrium. It i9 characterized by cella '~hich have abundant eosinophilic cytoplasm, bland vesicular nuclei, and cilia. These cells line gl ands. Benign squamous metaplasia may also occur in the endometrium, either in association with estrogen effect or in hyper plasia (3). Beni gn squamous me t aplasia has histologic similarities to morules except that intercellul ar bridges and/or keratin are present, which identify the cells as squamous. Lastly, since sheets of cells are present in morules, confusion with undifferentiated carcinoma of the endometrium is possibl e. Close examination of the process at high p~1er should o llm~ easy separation between morules and und ifferen tiated carcinoma . The etiology of morules i s not known. !~e have observed the pucess more frequently in women receiving exogenous estrogen therapy and there may be a relationship to hormone therapy. Morules hove been designated as squamous metaplasia because of the resemblance of t he calls to squamous cells . However, we think the term squamous metaplasia should be limited to those processes in \~hich the cells demonstrate keratin production and/or intercellular bridges. These are not found in intraglandular morules. The relationship of morules t o squomous metaplasia is unknown. The term adena acanthosis has also been suggested, but we do not like this term because of its similarity to adenoacanthoma (4) . Dutra has clearly de scrihcd morules arisinc from the columnar cells of tbe endothelial gl ands and suggested that t he process represents a manifes tation of the me taplasti c potential of the Mullerian epithelium of the endo metrium (5). l~e also think this is mos t likely o metaplastic process and do no t think it is related to neoplasia. There is no evidence that it is a pre-malignant process. The t erminolocy for carcinomas in the endometrium containing squamous epithelium is someHhat confused. The term adenoacanthoma, in my opinion, should not be used since it has been used both for those adenocarcinomas in which thare is bland or benign squamous metaplasia in association « ith t he adenocarcinoma, and for mixed adeno and squamous carcinoma. He prefer (74) Page 3 APRIL 21, 1974 - CASE NO. 21 ACCESSION NO. 20542 to label such tumors as adenocarcinoma with squamous metaplasia. Mixed carcinomas are composed of a combi nation of adenocarcinoma and squamous cell carcinoma (6). It is important to separate adenocarcinoma with squamous metaplasia- end mixed carcinomas, because the prognosis is con siderably different . In a recent study by Sil verberg of 148 cases of malignancy involving the endometrium, 48% were pure adenocarcinoma, 30% were adenocarcinoma wit h squamous metapl8aia, 17'% were mixed adeno- and squamous carcinoma, and 5'% were clear cell carcinoma (7). The prognosis for pure adenocarcinoma was 57% at five years, 83% at five years for adenocarcinoma with squamous metaplasia, and only 35% at five years for ~ed carcinomas, Mixed carcinomas have a poor prognosis, a greater incidence of invasion, and are seen in somel~hat older women . They hsve roughly the same prognosis as tha poorly differentiated and anaplastic carcinomas of the endometrium. For these reasons , adenocarcinoma with . sqoamous metaplasia, which has s n excellent prognosis shoul~ be1earofully and sharply separated from the mixed carcinomas. Both types of carcinoma should be separated from morules which are benign and associated with benign endometrium. REFERENCES: 1. ~fl1ite , A, J , et al,: Primary squamous cell carcinoma of the endometrium. Obatet . & Gyne col. 41:912, 1972, 2. Vellios, F.: Endometrial hy>erpl asias, precursors of endometrial carcinoma. Pathol, Ann . L:201, 1972. 3. Baggish, M.S . and lJoodruff, J . D.: The occurrence of squamous epithelium in the endometrium. Obstet. & Gynecol. Survey 22:69, 1967, 4 . Bomze, E.J. and Friedman, N. B. : Squamous metaplasia and adenoacanthosis of the endometri um , Obstet. & Gynecol. 30:619, 1967. 5, Dutra, F. R. : Intrag1andular morules of the endometr ium . Am, J, Clin. Path. 31:60 , 1959. 6. Ng, A.B. P., et al, : Mixed adenosquamous carcinoma of the endometrium. Am. J . Clin. Pathol, 59:765, 1973. 7. Silverberg, S.G. , et al.: Adenoacanthoma and mixed adenosquamous carcinoma of the endometrium. A cli.nicopathologic study, Cancer 30:1307, 1972. (75) APRIL 21, 1974 - CASE NO. 22 ACCESSION NO. 20525 MODERATOR'S DIAGNOSIS: Clear cell adenocarcinoma of the vagina. CLINICAL ABSTRACT: This 18 year old female presented with an 8 month hist.ory of premenstrual spotting followed by profuse vaginal bleeding. The patient's mother had received large doses of diethylstilbestrol for the treatment of o threatened miscarriage at l~weeks' gestation. Physical examination revealed a papillary mass with superficial necrosis in the upper third of the vagina on the right lateral wall. A total hysterectomy, partial vaginectomy, and lymph node dissection were performed. The vaginal tumor was dome-shaped measuring 1.5 x 1.5 em. and contained multiple cystic spaces. The lesion appeared limited to the superficial portion of the vagina. The remainder of the specimen was negative including the resected lymph nodes. MICROSCOPIC DESCRIPTION: The tumor is composed of a network of tubular structures lined by square to cuboidal cells with irregular prominent nuclei, many of which apparently are being extruded from the cella. Some of the cells are clear while others have pale eosinophilic cytoplasm. The tumor invades into the underlying stroma, Mitoses are frequent and the nuclei are hyperchromatic, irregular and cytologically atypical. Hucin is present in the spaces end in the cyto plasm of many of the tumor cells. Adjacent to the tumor, in some sections, are bland endocervical type glands consistent with adenosis vaginae. DISCUSSION: The tumor nm1 l Page 2 APRIL 21, 19·74 - CASE NO, 22 ACCESSION NO, 20525 Clear cell adenocarcinoma may have 3 different histologic patterns, One is tubular (parvolocular) in t~hich the tumor looks like renal tubules, the second is papillary and the third is solid sheets of tumor cells. l~ithin each of these three basic patterns there may be l'HO cell type.s: clear cells similar to those in renal cell carcinoma and cells with eosinophilic cytoplasm, The latter cells are the ones that most commonly demonstrate the extruded nuclei or hobnail appearance. These two cell types are almost always found mixed together in the same tumor but one may predominate, Some clear cell carcinomas, £or example, may resemble renal cell carcinoma. The most common histologic pattern is tubular, as is found in this case, <~ith the hobnail nuclei and scattered foci of clear cells. The cytoplasm of the tumor cells in the tubular form contain both glycogen and mucin and mucin is. often present in the lumens of the tubular structures. The tumors predominantly composed 'of clear cells have a better prognosis than those <~ith the tubular and papillary patterns, Clear cell adenocarcinoma occurs in the ovary, vagina, endometrium and cervix (4,5,6,7) . The relationship bet Another feature noted in the study by the clear cell carcinoma registry was an increase in adenosis vaginae in young women whose mothers received stilbestrol. lldenosis vagin.ae is the presence of Hullerian glands in the vagina <~hich may be lined ·by either endocervical or endometrial epithet'ium, The incidence of adenosis in young women whose mothers receival stilbestrol is around 70% in most series and as high as 90% in one culpomicroscopic series (10) . The common association of vaginal adenosis, and the occasional existence of transverse vaginal and cervical ridges in these young women , (77) Page 3 APRIL 21 , 1974 - CASE NO, 22 ACCESSION NO, 20525 provide morphologic evidence that stilbestrol causes disturbance of the development of the lowe r Mullerian tract. 1Yhether the clear cell adeno carcinoma develops from foci of adenosis or de novo is not entirely clear. For practical purposes young women with odenosia must be followed carefully to be sure they do not develop carcinoma. Large oreas of sdenosiD should be removed if possible and the smaller areas examined regularly. A recent update fran the adenocarcinoma registry to include 170 tots~ cases indicates that no asymptomatic pa t ient with clear cell carcinoma has thus far died of tumor. This emphasizes the importance of regularly examining CEymptomatic exposed patient~ and identifying such patients in the population. In the registry cases, 8~ of the patients who bed vaginal adenocarcinoma are ~live and 65% of those with cervical tumors are alive. The features which seem to be of most prognostic importance are the number of mitoses per 10 high power fields and the presence or absence of lymphatic invasion. A copy of the abstract from the registry, concerning the 170 cases to be published shortly, is attached following the references. Adenosi s vaginae may occur in women whose mothers have not been exposed to stilbestrol. In Sandberg's very careful autopsy study, adenosis was found in the vaginae of 9 of 35 women of al l different ages after puberty (11), Sandberg did not find adenosis in the prepubertal vagina. A more recent study has indicated that adenosis may be found in the vagina of infants in the first month of life but then is not found again until after puberty. These studies suggest hormonal influence in the development of adenosis vaginae. Adenosis vaginae must be differentiated from the mesonephric ducts (Gartner ' s ducts) which can be found in the lateral wall of the vagina, The mesonephric ducts are mucin negative whereas adenosis is positive for mucin, 1. Scully , R.E. and Barlow, J.P.: ''Mesonephroma" of the ovary. A tumor of Muller ian nature rel:~ted to the endometrioid carcinoma. cancer 20:1405, 1967 , 2. Allyn, D.L ., et al.: Endodtrmel sinus tumor of the vagina. Cancer 31: 1231, 1971. 3, Norris, R,S,, Bagley, G.P. and Taylor, H. B. : Carcinoma of the infant vagina. Arch, Psthol. 2Q:473, 1970, 4. Pine, G., et al.: Mesonephroms of tbe ovary. Cancer 1!:398, 1973. 5, Hameed, K. , et al.: Clear cell carcinoma of the ovary. Cancer 24:452, 1969. (78) Page 4 APRIL 21, 1974 - CASE NO. 22 ACCESSION NO. 20525 6, Tsukads, Y. , et al. : Clear-cell adenocarcinoma of the vagina. Three cases associated with maternal synthetic nonsteroid estrogen therapy. Cancer 29:1208, 1972. 7, Silverberg, S,G, and DeGiorgi, L. S. : Clear cell carcinoma of the vagina, A clinical, pathologic and electron microscopic study. Cancer ~:1680, 1972. 8, Herbst, A.L, and Scully, R,E,: Adenocarcinoma of the vasina in adolescence. Cancer ~:745, 1970, 9, Herbst, A.L. et al.: Clear-cell adenocarcinoma of the genital tract in young females, Registry report. N.E.J.M, 287:1259, 1972 . 10, Stofl, A, , et al.: Clinical diagnosis of vaginal adenosis. Obstet, & Gynecol. 43:118, 1974, 11. Sandberg. E. C. : The ~neidence ~nd distribution of occult V4~inal adenosis. 1\llleJ:, 3, Ooste~. & G.)lllecol, 101;324:, 1\161), (79) Page 5 APRIL 21, 1974 - cASE NO, 22 ACCESSION NO, 20525 CLEAR-CELL AOENOCARCINCI1A OF 'mE VAGINA AND CERVIX IN YOUNG FEMALES : AN ANALYSIS OF 170 REGISTRY CASES (By Herbst, A,L, , Scully, R.E. , and Robboy, S. to be published in Amer, J, Obstet, and Gynecol. , 1974) Abstract: One hundred cases of vaginal and 70 cervical adenocarcinomas from the Registry of Cl ear- Cell Adenocar cinoma of the Genital Tract in Young Females have been analyzed. The age range of the patients was 7 to 29 years and the frequent association with prenatal exposure to diethylstilbestrol and similar non-steroidal estrogens was confirmed, The hormone admirdstration began prior to the 18th week of pregnancy end was continued for periods ranging from 1 week to almost the entire length of the pregnancy. The total dosages ranged from 300 to 18,200 mg. Although moat patients had vaginal bleeding or discharge, 16 percent were asymptomatic, Abnormel cytology was the first clue to the diagnosis of cancer in 11 patients, but 21 percent of the smears were negative, The larger and more deeply invasive tumors 1~ere often complicated by lymph node metastases, but these were a l so encountered in 1 case in which the tumor had on area of only 3 cm2 and with another tumor that invaded less than 3 mm. These findings suggest that local treatment of the pr imary tumor alone may be inadequate in some cases, Recurrences have developed in 37 of the patients and 2A of them have died, al though the follow up in one • third of the caaes has been less than t1-1o years, The recurrences frequently involved the lungs end supraclavicular lymph nodes as well as the pelvis. The very common association of vaginal sdenosis end the occasional co-existence of transverse vaginal or cervical ridges provic!o morphologic evidence of a stilbestrol-related disturbance in the development of the lower Mullerian tract, The results of intravenous pyelograp~suggest that the development of the urinary tract is not affected. The fact that ell the asymptomatic patients with carcinoma have been successfully treated thus far underscores the importance of screening exposed asymptomatic patients in search of early cases, The rarity (9 percent) of these cancers prior to the age of tl-lelve years, auggeststhat the inclusion of a large population of girls in this ago group in a screening program would uncover very few cases, Such individuals should certainl y be examined , h~~ever, at any time abnormal vaginal bleeding or discharge develops. tBO) APRIL 21, 1974 - CASE NO, 23 ACCESSION NO. 20528 MODERATOR'S DIAGNOSIS: Low grade fibrosarcana of the ovary CLINICAL ABSTRACT: Tbis 18 year old female was found to have a large pelvic mass displacing the uterus. At operation the right ovary was replaced by a solid tumor which demonstrated extensive hemorrhagic necrosis in ell areas except the periphery, The viable peripheral portions were pale-gray to slightly yellow end semi translucent. MIRCOSCOPIC DESCRIPTION: This is a fibrous tumor of variable cellularity composed of elongate cells with generally spindled nuclei end fine chromatin. There is minimal atypia, but up to 5 to 6 mitoses per 10 high power field can be found, Hyaline plagues are also present, Some of the tumor cells are more cuboidal with rather abundant cytoplasm. A reticulin stain shows reticulin around individual cells. The trichrome stain indicates large amounts of collagen without smooth muscle staining pattern, Longitudinal grooves are not noted in the nuclei, A mucin stain is negative, DISCUSSION: The differential diagnosis of this tumor included fibrosarcoma , atypical fibroma with large numbers of mitoses, thecoma, leiomyoma, Krukenberg tumor and massive edema of the ovary. The latter entity is characterized by marked enlargement of the ovary be edema;·. fluid with retention of follicular structures (l). These features are not ?resent in this cose. Mucin stains in this case ere negative and there is no evidenco of metastatic carcinoma, The trichrome stain does not indicate the presence of smooth muscle. This tumor then brings up two problens in diagnosis, nemely, ·what are the criteris for the diagnosis of thecoms versus fibroma, and what are the criteria for the determining malignancy in fibromas and thecomas? Thecomas are tumors derived from the undifferentiated ovarian sex cord mesenchyme (2) . Hhen sufficiently differentiated to blend with granulosa cell t umor or to shaw evidence of luteinization and estrogen production, they are easy to diagnose. On the other end of the spectrum the tumor cells may be spindled and have cbaracteriatice of fibrous tissue as stromal celle do in the normal ovary. Where thecoma ends and fibroma begi.ns is difficult to determine for many tumors. It is probable that both thecoma and fibroma represent parts of a spectrum of sex cord stromal neoplasms and that thecoms is composed of stromal cells which are producing hormones (3). In the classio examples, fibroms contains interlacing whorls of thin spindle celle with small dark nuclei and (81) Page 2 APRIL 21, 1974 - CASE NO. 23 ACCESSION NO. 20528 occasional hyaline formation whereas thecoma is most frequently composed of fusiform cells with pale cytoplasm, large pale nuclei and foci of luteiniza tion. The cells in thecoma frequently contain lipid. H~ Determination of a malignant criteria is also difficult . For practical purposes, thecomas are benign and I think reports of malignant varieties are open to question (2,4). As far as I know there have been no reports of biologically malignant tumors containing lipid cells which produce estrogen and morphologically look like thecoma. H~ever, there are malignant spindle tumors arising in the ovary which do not function and have been considered to be fibrosarcomas. Thus, in my opinion, thecoma is s benign tumor and there have been no acceptable reports of malignant varieties. On the other hand, lh~re are rare malignant spindle celled neoplasms in the ova~y which do not function, ~ It is also difficult to determine where to draw the l ine be~ REFERENCES : l. Kaloton~,C . E., et ol.: Massive edema ·of the ovary simulating fibroma . Obstet. & Gynccol. 1i:564, 1969. 2. Scully, R.E.: Recent progress in ovarian cancer. Hum. Pathol.,l:73, 1970. 3. Amin. H.K., Okagaki, T. and Richart, R.: Classification of fibroma and thecoma of the ovary. An ultrastructural study. Cancer 27:~38, 1971. 4. N~•ris, H. J. and Taylor, H. B.: Prognosis of granulosa-theca tumors of the ovary. Cancer 21:255, n96S. {82) APRIL 21, 1974 - CASE NO. 24 ACCESSION NO. 20526 MODER/I TOR'S DIAGNOSIS: Squamous papilloma ("Cockscomb polyp'') of the cervix associated with pregnancy. CLINICAL ABSTR/ICT: This 20 year old gravida 11, para I patient had a 5-6 month history of post-coital bleeding, and an atypical cytology early in her pregnancy. Pelvic examination revealed two discoid lesions over the cervix. A cone was performed and grossly the specimen revepled most of the epithelial surface to be replaced by a velvety, smewhat papillary, lesion which in some areas was plaque like. The tumor mass uas rather granular, pale yellow and elevated to 1.5 em. above the background of the smooth portion of the epithelium. MICROSCOPIC DESCRIPTION: The epithelium of the cervix has been thrown up into papillary f~onds lined by multilayered but orderly squamous epithelium. Most of the cells are rather basaloid and somewhat immature, but more mature squamous epithelium is also present on the papillary stalks. Remnants of the endocervical glands can be seen between the squamous elements. The stalks of the papillary fronds are composed of delicate connective tissue containing blood vessels. Focal areas of chronic inflammation are present. Hyperkeratosis and paralooratosis are not conspicuous and vacuolated cells are not seen. DISCUSSION: The squamous papillomas of the cervix include , besides the cockscomb polyp, condyloma accuminata and the "true" papilloma of !Wrt'. ~ and Gore ~1 ,2, 3). Verrucous squamous carcinoma must also be included in the differential diagnosis (4,5) . Cockscomb polyp is of unknown etiology and is found only during pregnancy. It is e warty, firm, usually single, lesion which grows rapidly during pregnancy but regresses spontaneously in the post partum period (1). It is not malignant or premalignant and has no relationship to squamous cell carcinoma. As soon as carcinoma is ruled out by biopsy, tbe lesion need not be further treated. The tumor cells are usually not vacuoln rad. Condyloma eccuminata is composed of multiple soft elevated masses of squamous epithelium of variable size and shape. It can be small or quite massive. Microscopically there is a complicated papillary arrangement of well differentiated and usually orderly squamous epithelium supported by delicate vascular connective tissue stalks, Focally, there is vacuolization of the squamous cells and a lymphocytic infiltrate in the underlying dermis or submucosa is a regular feature. Condyloma accuminata may also contain atypical cella, but full thickness atypia is not seen and the degree of atypia found in carcinoma-in-situ ia not present. Hertig and Gore described "true" squamous papilloma as occurring in non-pregnant women usually after the (83) Page 2 lAPRlL 21, 1974 - CASE NO, 24 . ACCESS~ON NO. 20526 menopause (3) . It is a single small lesion 2 to 4 mm. broad basad and composed of squamous cells. It grows progressively larger and may be premalignant, This is an extremely rare form of squamous papilloma of the cervix. Verrucous carcinoma must be separated from the squamous papillary lesions of the cervix. On the one hand, verrucous carcinoma should be recognized as a carcinoma and not a papilloma since it is capable of local aggressive growth which can result in the .death of the patient (4,5). On tha.other hand, it is also important not to confuse verrucous squamous carcinoma with invasive squamous carcinoma of the usual type since verrucous carcinoma may become more anaplastic and metastasize if irradiated (6). Verrucous carcinoma is a fungating verruciform l esion with bulbous rounded ends of squamous epithelium protruding into the underlying stroma. ayperkeratosis and parakeratosis are prominent and the squamous cells have pale staining eosinophilic cytoplasm. Chronic inflammation ia invariable and mitoses and atypia may be present. Verrucous carcinoma can easily be misdiagnosed as condyloma accuminata histologically, and one should never diagnose s benign squamous papilloma of the cervix without l 1, Simcock, M.J.: Papillomas of the uterine cervix. Auat. N.Z.J. Obstet, Gynecol . i:l74, 1964 . 2, Gilbert, T.P. and Palladino, A. : Squamous papillomas of the uterine cervix, Amer. J. Clin. Pathol, 46:115, 1966. 3. Hertig, A.T, and Gore , B.: Tumors of the female sex organ.s, Pert 2, Tumors of the vulva, vagina and uterus. A.F.I .'J>. Sec. 9; Pas. 33:90, 1960. 4. Kraus , P,T. and Perez~iesa, C,: Verrucous carcinoma. Clinical and pathologic study of 105 cases involving oral cavity, larya¥ and genitalia. Cancer 19:26, 1966, 5. Jennings, R.H. and Barclay, D,L.: Verrucous carcinoma of the cervix. Cancer 2Q:430, 1972. 6. Oemian, S. D.P., et al.: Perineural invesian and anaplastic transformation of verrucous carcinoma. Cancer ~:395, 1973. (84) APRIL 21, 1974 - CASE NO. 25 ACCESSION NO. 20527 MODERATOR'S DIAGNOSIS: Serous tumor of borderline malignancy (low malignant potential) of the ovary CLINICAL ABSTRACT: This L,7 year old female was first noted to have an abdominal mass during an admission for replacement ~f aortic, mitral and tricuspid valves. Follow ing her cardiac surgery abe \·Ia& referred to a gynecologist but did not go to him for a year. By that time the mass had gr~>n considerably larger. At laparotomy there was a smooth cystic mass occupying the left adne~a. There was no evidence of tumor on the outside of the cyst and no evidence of tumor elsewhere in the pelvis or in the abdomen. On cut section, the interior of the cyst contained sticky thick fluid and ~1as U .ned by innumerable · yel101~ pinlt papillae varyin:; from 0.5 to 2.0 em. in heieht. MICROSCOPIC DESCRIPTION: This P8P.illary tumor is composed of columnar to cuboidal cells lining club shaped and oft.en edematous papillae. The tumor cells have rather abundant eosinophilic cytoplasm and in many areas the cells are stratified to a heieht of t, or 5 nuclei. As many as 4 mitoses can be mund in o single hi&h power field . Most o·f the nuclei are rather vesicular and bland but occasional cells have prominent eosinophilic nucleoli . Nuclear outlines are sli&h~ly irregular. Many of the rspillae are edematous and club shaped but there ia no evi dence of stromal invasion in any area. DISCU~: Included in the surface (coelomic) epithelial neoplasms of the ovary ore the serous, mucinous, endometrioid, Brenner, clear cell and malignant mixed Mullerian tumors (1, 2) • For each of these tumor types, e~cept the malignant mixed Mullerian tumor, there i s a benign form, a borderline malignant form and o frankly malignant form (2, 3) . In practice, this classification of benf.En, borderline malig>iant and malienant works '~ell for the serous neoplasms, reasonably well for the mucinous neoplaams and is somewhat difficult to apply to the clear cell carcinomas and endometrioid carcinoma (4,5), The borderline variety of Brenner tumors is the prolifera tine tumor which has been benign in all the cases thus far reported, For the serous and mucinous neoplasms, the three different crades of tumors should be recoenized and diagnosed since prognosis and therapy will vary. Histologic criteria for diaenosing serous cyatadenom.a and mucinous cystadenoma sre well known. The borderline tumors are characterized by epithelial cell proliferative. activity, nuclear atypia, mitoses and nuclear (85) Page 2 APRIL 21, 1974 - CASE NO . 25 ACCESSION NO. 20527 stratification (1), Adenomas may have minor degrees of atypia and focal areas of minor stratification, but when stratification becomes extensive and more than 1 or 2 nuclei, the tumor should be considered to be borderline (low malignant potential). Borderline tumors may implant on the peritoneum and rarely metastases can occur, but'•both events are unusual. The borderline tumors must be evaluated exclusively on examination of the ovarian tumor and not on the basis of spread to the pelvie (2) . The validity of this diagnostic approach has been demonstrated by the better survival of the patients with borde·£Une serous tumors, even those that have spread beyond the ovary, as compared to patients with frank carcinoma. The histologic criteria for diagnosing carcinoma is stromal invasion. This criteria works well in the serous group of neoplasms and serous carcinoma should not be diagnosed unless invasion of the stroma can be demonstrated. One must be cautious not to misdiagnose glandular extensions into the stroma and complex glandular growth patterns as stromal invasion. The criteria of invasion is leas reliable for the mucinous tumors because of the complexity of their growth pattern, A recent study ~~ Hart and Norris indicates that mucinous tumors with nuclear stratification greater than 3 nuclei should be considered carcinoma while those with less stratification arc borderline or benign neoplasms (6), In our experience, this criteria is extemely helpful, For the endometrioid tumors the borderline category is extremely unusual and would be represented by markedly atypical adenomatous hyperplasia in endometriosis. Instead of using the borderline category, we grade the endometrioid carcinomas from 1 to 4 using the sam9 histologic criteria we use for corpus carcinomas. We have not found the borderline category to be of value in the clear cell carcinomas and it is obviously not pertinent for the mixed Mulletian tumors. The serous tumor of borderline malignancy represent an important, and rather large, group of ovarian tumors and they should be recognized diagnos tically. Borderline tumors should be separated from carcinoma and strict criteria used for their diegnosi.a. Characteristically, borderline serous tumors are cystic and the cysts are lined by broad club shaped papillae with edematous stroma as demonstrated in this case. Nuclear stratification is usually marked and mitoses may be numerous but invasion is absent, In most series the survival of borderline serous carcinoma is more than 85~ for five years whereas the survival in serous carcinQDS is usually leu than 201; in five yesrs. Because of this difference in prognosis, we think that ~atients with borderline serous neoplasm& confined to the ovary can be treated by surgery alone without post- operative irradiation (7) , In addition, even if patients should have recurrence of a bord.. rline tumor, it is usually limited to local pelvic spread which grows very el owly often after long periode. of time. Pelvic extension of borderline tumors may spontaneously regress after (86) Page 3 APRIL 21, 1974 - CASE NO. 25 ACCESSION NO. 20527 the primary is re111oved . For mucinous t=ora, the difference in prognosis is less striking, par ticularly if one uses only the criteria of invasion to diagnose malignancy. However, we think the borderline category should be recognized and the criteria of Hart and Norris utilized. In summary, borderline serous and 111ucinous neoplasms have biologic behavior and histol ogic patrerna which are significantly different from frank carcinoma and f rom the adenomas to all~1 recog11ition and separation. t~e t hink it illlportant for purposes of prognosis and future therapy to diagnose this group of neoplasms accurately, The separation into 3 types of tumors has been recognized by both FIGO and the World Health Organization in the new cl~asification of ovarian neoF:asms. Criteria are easily applied for the serous and 111oat of the mucinous tUIIIors, 1·1hereas it is less useful for the endometrioid and clear cell tumors. RBFEIU!NCES : l . Scully, R.E.: Recent progr ess in ovarian cancer, Hum . Path. !:73, 1970. 2. Serov. S.P. and Scully, R.E. : His tological typing of ovarian tumors. Geneva, 1973. ~lorld Health Organt•at ion. \ 3 , Gondos, B.: Electron microscopic study of papillary serous tumors of t be ovary. Cancer ~ : 1 455, 1971 . l>. Czernobilaky, B, , et al.: Clear cell carci noma of tho ovary. A clinicopathologic analysis of pure and mixed forma and comparison with endometrioid carcinoma. Cancer 25:762, 1970. 5, Czornobilsky, B., et al. : Endcmetrioid carcinoma of the ovary. Cancer 26:1141 , 1970. 6, Hart, W. R. and Norris, H,J. : Borderline and malignant. mucinous tumors of the ovary. Cancer 31:1031, 1973. 7. Hintz, B.L ., Pules, z . , Kempson, R.L,, et al,: Results of postoperative megavol t age radiotherapy of malignant surface epithelial tumors of the ovary. In press: Radiology,